TY - JOUR AU - Huang, Peng AU - Qu, Chaoyi AU - Rao, Zhijian AU - Wu, Dongzhe AU - Zhao, Jiexiu TI - Bidirectional regulation mechanism of TRPM2 channel: role in oxidative stress, inflammation and ischemia-reperfusion injury JF - FRONTIERS IN IMMUNOLOGY J2 - FRONT IMMUNOL VL - 15 PY - 2024 SP - 01 EP - 17 PG - 17 SN - 1664-3224 DO - 10.3389/fimmu.2024.1391355 UR - https://m2.mtmt.hu/api/publication/35182188 ID - 35182188 AB - Transient receptor potential melastatin 2 (TRPM2) is a non-selective cation channel that exhibits Ca 2+ permeability. The TRPM2 channel is expressed in various tissues and cells and can be activated by multiple factors, including endogenous ligands, Ca 2+ , reactive oxygen species (ROS) and temperature. This article reviews the multiple roles of the TRPM2 channel in physiological and pathological processes, particularly on oxidative stress, inflammation and ischemia–reperfusion (I/R) injury. In oxidative stress, the excessive influx of Ca 2+ caused by the activation of the TRPM2 channel may exacerbate cellular damage. However, under specific conditions, activating the TRPM2 channel can have a protective effect on cells. In inflammation, the activation of the TRPM2 channel may not only promote inflammatory response but also inhibit inflammation by regulating ROS production and bactericidal ability of macrophages and neutrophils. In I/R, the activation of the TRPM2 channel may worsen I/R injury to various organs, including the brain, heart, kidney and liver. However, activating the TRPM2 channel may protect the myocardium from I/R injury by regulating calcium influx and phosphorylating proline-rich tyrosine kinase 2 (Pyk2). A thorough investigation of the bidirectional role and regulatory mechanism of the TRPM2 channel in these physiological and pathological processes will aid in identifying new targets and strategies for treatment of related diseases. LA - English DB - MTMT ER - TY - JOUR AU - Joshi, Nishit AU - Vaidya, Bhupesh AU - Sharma, Shyam Sunder TI - Transient receptor potential channels as an emerging target for the treatment of Alzheimer's disease: Unravelling the potential of pharmacological interventions JF - BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY J2 - BASIC CLIN PHARMACOL PY - 2024 PG - 26 SN - 1742-7835 DO - 10.1111/bcpt.14073 UR - https://m2.mtmt.hu/api/publication/35313952 ID - 35313952 LA - English DB - MTMT ER - TY - JOUR AU - Alexandris, A.S. AU - Koliatsos, V.E. TI - NAD+, Axonal Maintenance, and Neurological Disease JF - ANTIOXIDANTS & REDOX SIGNALING J2 - ANTIOXID REDOX SIGNAL VL - in press PY - 2023 SN - 1523-0864 DO - 10.1089/ars.2023.0350 UR - https://m2.mtmt.hu/api/publication/34191665 ID - 34191665 N1 - Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, United States Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, United States Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States Export Date: 12 October 2023 CODEN: ARSIF Correspondence Address: Alexandris, A.S.; Department of Pathology, Ross Research Building, Room 558, 720 Rutland Avenue, United States; email: aalexa27@jh.edu Correspondence Address: Koliatsos, V.E.; Department of Pathology, Ross Research Building, Room 558, 720 Rutland Avenue, United States; email: koliat@jhmi.edu AB - Significance: The remarkable geometry of the axon exposes it to unique challenges for survival and maintenance. Axonal degeneration is a feature of peripheral neuropathies, glaucoma, and traumatic brain injury, and an early event in neurodegenerative diseases. Since the discovery of Wallerian degeneration (WD), a molecular program that hijacks nicotinamide adenine dinucleotide (NAD+) metabolism for axonal self-destruction, the complex roles of NAD+ in axonal viability and disease have become research priority. Recent Advances: The discoveries of the protective Wallerian degeneration slow (WldS) and of sterile alpha and TIR motif containing 1 (SARM1) activation as the main instructive signal for WD have shed new light on the regulatory role of NAD+ in axonal degeneration in a growing number of neurological diseases. SARM1 has been characterized as a NAD+ hydrolase and sensor of NAD+ metabolism. The discovery of regulators of nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) proteostasis in axons, the allosteric regulation of SARM1 by NAD+ and NMN, and the existence of clinically relevant windows of action of these signals has opened new opportunities for therapeutic interventions, including SARM1 inhibitors and modulators of NAD+ metabolism. Critical Issues: Events upstream and downstream of SARM1 remain unclear. Furthermore, manipulating NAD+ metabolism, an overdetermined process crucial in cell survival, for preventing the degeneration of the injured axon may be difficult and potentially toxic. Future Directions: There is a need for clarification of the distinct roles of NAD+ metabolism in axonal maintenance as contrasted to WD. There is also a need to better understand the role of NAD+ metabolism in axonal endangerment in neuropathies, diseases of the white matter, and the early stages of neurodegenerative diseases of the central nervous system. © Athanasios S. Alexandris and Vassilis E. Koliatsos, 2023; Published by Mary Ann Liebert, Inc. LA - English DB - MTMT ER - TY - JOUR AU - Okada, Y. AU - Numata, T. AU - Sabirov, R.Z. AU - Kashio, M. AU - Merzlyak, P.G. AU - Sato-Numata, K. TI - Cell death induction and protection by activation of ubiquitously expressed anion/cation channels. Part 3: the roles and properties of TRPM2 and TRPM7 JF - FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY J2 - FRONT CELL DEV BIOL VL - 11 PY - 2023 SN - 2296-634X DO - 10.3389/fcell.2023.1246955 UR - https://m2.mtmt.hu/api/publication/34221622 ID - 34221622 N1 - Export Date: 27 October 2023 Correspondence Address: Okada, Y.; National Institute for Physiological Sciences (NIPS)Japan; email: okada@nips.ac.jp AB - Cell volume regulation (CVR) is a prerequisite for animal cells to survive and fulfill their functions. CVR dysfunction is essentially involved in the induction of cell death. In fact, sustained normotonic cell swelling and shrinkage are associated with necrosis and apoptosis, and thus called the necrotic volume increase (NVI) and the apoptotic volume decrease (AVD), respectively. Since a number of ubiquitously expressed ion channels are involved in the CVR processes, these volume-regulatory ion channels are also implicated in the NVI and AVD events. In Part 1 and Part 2 of this series of review articles, we described the roles of swelling-activated anion channels called VSOR or VRAC and acid-activated anion channels called ASOR or PAC in CVR and cell death processes. Here, Part 3 focuses on therein roles of Ca2+-permeable non-selective TRPM2 and TRPM7 cation channels activated by stress. First, we summarize their phenotypic properties and molecular structure. Second, we describe their roles in CVR. Since cell death induction is tightly coupled to dysfunction of CVR, third, we focus on their participation in the induction of or protection against cell death under oxidative, acidotoxic, excitotoxic, and ischemic conditions. In this regard, we pay attention to the sensitivity of TRPM2 and TRPM7 to a variety of stress as well as to their capability to physicall and functionally interact with other volume-related channels and membrane enzymes. Also, we summarize a large number of reports hitherto published in which TRPM2 and TRPM7 channels are shown to be involved in cell death associated with a variety of diseases or disorders, in some cases as double-edged swords. Lastly, we attempt to describe how TRPM2 and TRPM7 are organized in the ionic mechanisms leading to cell death induction and protection. Copyright © 2023 Okada, Numata, Sabirov, Kashio, Merzlyak and Sato-Numata. LA - English DB - MTMT ER - TY - JOUR AU - Szöllősi, András AU - Almássy, János TI - Functional characterization of the transient receptor potential melastatin 2 (TRPM2) cation channel from Nematostella vectensis reconstituted into lipid bilayer JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 10 SN - 2045-2322 DO - 10.1038/s41598-023-38640-6 UR - https://m2.mtmt.hu/api/publication/34064647 ID - 34064647 N1 - Department of Biochemistry, Semmelweis University, Tuzolto u. 37-47, Budapest, 1094, Hungary Department of Physiology, Semmelweis University, Tuzolto u. 37-47, Budapest, 1094, Hungary ELKH-SE Ion Channel Research Group, Semmelweis University, Tuzolto u. 37-47, Budapest, 1094, Hungary HCEMM-SE Molecular Channelopathies Research Group, Semmelweis University, Tuzolto u. 37-47, Budapest, 1094, Hungary Export Date: 4 September 2023 Correspondence Address: Szollosi, A.; Department of Biochemistry, Tuzolto u. 37-47, Hungary; email: szollo5@gmail.com Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium, 7440-70-2, 14092-94-5; Adenosine Diphosphate Ribose; Calcium; Cations; Lipid Bilayers; TRPM Cation Channels Funding details: 739593 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, KKP 144199 Funding text 1: This work was supported by Semmelweis Science and Innovation Fund STIA_18_M; EU Horizon 2020 Research and Innovation Program grant 739593 and National Research, Development and Innovation Fund grant KKP 144199. We thank László Csanády for funding and thorough reading and comments on the manuscript. We thank Balázs Tóth for help with poly- l -lysine measurements and stimulating discussions. AB - Transient receptor potential melastatin 2 (TRPM2) cation channel activity is required for insulin secretion, immune cell activation and body heat control. Channel activation upon oxidative stress is involved in the pathology of stroke and neurodegenerative disorders. Cytosolic Ca 2+ , ADP-ribose (ADPR) and phosphatidylinositol-4,5-bisphosphate (PIP 2 ) are the obligate activators of the channel. Several TRPM2 cryo-EM structures have been resolved to date, yet functionality of the purified protein has not been tested. Here we reconstituted overexpressed and purified TRPM2 from Nematostella vectensis (nvTRPM2) into lipid bilayers and found that the protein is fully functional. Consistent with the observations in native membranes, nvTRPM2 in lipid bilayers is co-activated by cytosolic Ca 2+ and either ADPR or ADPR-2′-phosphate (ADPRP). The physiological metabolite ADPRP has a higher apparent affinity than ADPR. In lipid bilayers nvTRPM2 displays a large linear unitary conductance, its open probability (P o ) shows little voltage dependence and is stable over several minutes. P o is high without addition of exogenous PIP 2 , but is largely blunted by treatment with poly- l -Lysine, a polycation that masks PIP 2 headgroups. These results indicate that PIP 2 or some other activating phosphoinositol lipid co-purifies with nvTRPM2, suggesting a high PIP 2 binding affinity of nvTRPM2 under physiological conditions. LA - English DB - MTMT ER - TY - JOUR AU - Martucci, L.L. AU - Cancela, J.-M. TI - Neurophysiological functions and pharmacological tools of acidic and non-acidic Ca2+ stores JF - CELL CALCIUM J2 - CELL CALCIUM VL - 104 PY - 2022 SN - 0143-4160 DO - 10.1016/j.ceca.2022.102582 UR - https://m2.mtmt.hu/api/publication/32917618 ID - 32917618 N1 - Export Date: 4 July 2022 CODEN: CECAD Correspondence Address: Martucci, L.L.; Department of Pharmacology, Mansfield Road, United Kingdom; email: lora.martucci@new.ox.ac.uk Chemicals/CAS: 1,4 dihydro 2,6 dimethyl 5 nitro 4 [2 (trifluoromethyl)phenyl] 3 pyridinecarboxylic acid methyl ester, 71145-03-4; 2 aminoethoxydiphenylborane, 524-95-8; 2,5 di tert butylhydroquinone, 88-58-4; amitriptyline, 50-48-6, 549-18-8; amlodipine, 88150-42-9; bafilomycin A1, 88899-55-2; benzocaine, 1333-08-0, 94-09-7; bepridil, 64706-54-3, 68099-86-5; caffeine, 58-08-2; calcium ion, 14127-61-8; chlorpromazine, 50-53-3, 69-09-0; cinchocaine, 61-12-1, 8061-94-7, 85-79-0; clomifene, 911-45-5; clomipramine, 17321-77-6, 303-49-1; cyclic adenosine diphosphate ribose, 119340-53-3; cyclopiazonic acid, 18172-33-3, 83136-88-3; dantrolene, 14663-23-1, 7261-97-4, 24868-20-0; desipramine, 50-47-5, 58-28-6; diltiazem, 33286-22-5, 42399-41-7; egtazic acid, 67-42-5; ethylene glycol 1,2 bis(2 aminophenyl) ether n,n,n',n' tetraacetic acid, 73630-08-7; etidocaine, 36637-18-0, 36637-19-1; felodipine, 72509-76-3; fluphenazine, 146-56-5, 69-23-8; imipramine, 113-52-0, 50-49-7; isradipine, 75695-93-1, 88977-22-4; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; mepivacaine, 1722-62-9, 96-88-8; naringenin, 480-41-1, 67604-48-2; nicardipine, 54527-84-3, 55985-32-5; nicotinic acid adenine dinucleotide phosphate, 5502-96-5; nifedipine, 21829-25-4; nimodipine, 66085-59-4; nitrendipine, 39562-70-4; nortriptyline, 72-69-5, 894-71-3; oxodipine, 90729-41-2; pimozide, 2062-78-4; prilocaine, 1786-81-8, 721-50-6; procaine, 51-05-8, 59-46-1; raloxifene, 82640-04-8, 84449-90-1; retinoic acid, 302-79-4; rhein, 478-43-3; riluzole, 1744-22-5; ryanodine, 15662-33-6; tetracaine, 136-47-0, 94-24-6; tetrandrine, 518-34-3; thapsigargin, 67526-95-8; triflupromazine, 1098-60-8, 146-54-3; trimecaine, 1027-14-1, 616-68-2; verapamil, 152-11-4, 52-53-9; veratridine, 71-62-5; xestospongin C, 88903-69-9; calcium, 7440-70-2, 14092-94-5; nicotinamide adenine dinucleotide phosphate, 53-59-8; Calcium; NADP; Ryanodine Receptor Calcium Release Channel Tradenames: bay k 8644; bz 194; cz 48; jnj 16259685; ml sa 1; ml si 1; mt 08; ned 19; sg 005; sg 094; um 09 Funding details: Oxford University Funding details: Centre National de la Recherche Scientifique, CNRS Funding text 1: LLM research is funded by Oxford University. JMC research is funded by the CNRS. Images were created using biorender.com. AB - Ca2+ signalling is of prime importance in controlling numerous cell functions in the brain. Endolysosomes are acidic organelles currently emerging as important Ca2+ stores in astrocytes, microglia, endothelial cells, and neurons. In neurons, these acidic Ca2+ stores are found in axons, soma, dendrites, and axon endings and could provide local sources of Ca2+ to control synaptic transmission, neuronal plasticity, and autophagy to name a few. This review will address how acidic Ca2+ stores are recruited in response to cell stimulation. We will focus on the role of the endolysosomal two-pore channels (TPCs) and their physiological agonist nicotinic acid adenine dinucleotide phosphate (NAADP) and how they interact with cyclic ADP-ribose and ryanodine receptors from the endoplasmic reticulum. Finally, this review will describe new pharmacological tools and animal mutant models now available to explore acidic Ca2+ stores as key elements in brain function and dysfunction. © 2022 LA - English DB - MTMT ER - TY - JOUR AU - Petroianu, G.A. TI - Hyperthermia and Serotonin: The Quest for a “Better Cyproheptadine” JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 6 SN - 1661-6596 DO - 10.3390/ijms23063365 UR - https://m2.mtmt.hu/api/publication/32917620 ID - 32917620 N1 - Cited By :2 Export Date: 4 July 2022 Correspondence Address: Petroianu, G.A.; College of Medicine & Health Sciences, United Arab Emirates; email: georg.petroianu@ku.ac.ae AB - Fine temperature control is essential in homeothermic animals. Both hyper-and hypothermia can have deleterious effects. Multiple, efficient and partly redundant mechanisms of adjusting the body temperature to the value set by the internal thermostat exist. The neural circuitry of temperature control and the neurotransmitters involved are reviewed. The GABAergic inhibitory output from the brain thermostat in the preoptic area POA to subaltern neural circuitry of temperature control (Nucleus Raphe Dorsalis and Nucleus Raphe Pallidus) is a function of the balance between the (opposite) effects mediated by the transient receptor potential receptor TRPM2 and EP3 prostaglandin receptors. Activation of TRPM2-expressing neurons in POA favors hypothermia, while inhibition has the opposite effect. Conversely, EP3 receptors induce elevation in body temperature. Activation of EP3-expressing neurons in POA results in hyperthermia, while inhibition has the opposite effect. Agonists at TRPM2 and/or antagonists at EP3 could be beneficial in hyperthermia control. Activity of the neural circuitry of temperature control is modulated by a variety of 5-HT receptors. Based on the theoretical model presented the “ideal” antidote against serotonin syndrome hyperthermia appears to be an antagonist at the 5-HT receptor subtypes 2, 4 and 6 and an agonist at the receptor subtypes 1, 3 and 7. Very broadly speaking, such a profile translates in a sympatholytic effect. While a compound with such an ideal profile is presently not available, better matches than the conventional antidote cyproheptadine (used off-label in severe serotonin syndrome cases) appear to be possible and need to be identified. © 2022 by the author. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - JOUR AU - Alexander, Stephen P. H. AU - Mathie, Alistair AU - Peters, John A. AU - Veale, Emma L. AU - Striessnig, Jorg AU - Kelly, Eamonn AU - Armstrong, Jane F. AU - Faccenda, Elena AU - Harding, Simon D. AU - Pawson, Adam J. AU - Southan, Christopher AU - Davies, Jamie A. AU - Aldrich, Richard W. AU - Attali, Bernard AU - Baggetta, Austin M. AU - Becirovic, Elvir AU - Biel, Martin AU - Bill, Roslyn M. AU - Catterall, William A. AU - Conner, Alex C. AU - Davies, Paul AU - Delling, Markus AU - Di Virgilio, Francesco AU - Falzoni, Simonetta AU - Fenske, Stefanie AU - George, Chandy AU - Goldstein, Steve A. N. AU - Grissmer, Stephan AU - Ha, Kotdaji AU - Hammelmann, Verena AU - Hanukoglu, Israel AU - Jarvis, Mike AU - Jensen, AndersA AU - Kaczmarek, Leonard K. AU - Kellenberger, Stephan AU - Kennedy, Charles AU - King, Brian AU - Kitchen, Philip AU - Lynch, Joseph W. AU - Perez-Reyes, Edward AU - Plant, Leigh D. AU - Rash, Lachlan AU - Ren, Dejian AU - Salman, Mootaz M. AU - Sivilotti, Lucia G. AU - Smart, Trevor G. AU - Snutch, Terrance P. AU - Tian, Jinbin AU - Trimmer, James S. AU - Van den Eynde, Charlotte AU - Vriens, Joris AU - Wei, Aguan D. AU - Winn, Brenda T. AU - Wulff, Heike AU - Xu, Haoxing AU - Yue, Lixia AU - Zhang, Xiaoli AU - Zhu, Michael TI - The concise guide to pharmacology 2021/22: Ion channels JF - BRITISH JOURNAL OF PHARMACOLOGY J2 - BR J PHARMACOL VL - 178 PY - 2021 SP - S157 EP - S245 PG - 89 SN - 0007-1188 DO - 10.1111/bph.15539 UR - https://m2.mtmt.hu/api/publication/32358900 ID - 32358900 N1 - Supplement: 1 AB - The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate. LA - English DB - MTMT ER - TY - JOUR AU - Gattkowski, E. AU - Rutherford, T.J. AU - Möckl, F. AU - Bauche, A. AU - Sander, S. AU - Fliegert, R. AU - Tidow, H. TI - Analysis of ligand binding and resulting conformational changes in pyrophosphatase NUDT9 JF - FEBS JOURNAL J2 - FEBS J PY - 2021 SN - 1742-464X DO - 10.1111/febs.16097 UR - https://m2.mtmt.hu/api/publication/32188279 ID - 32188279 N1 - The Hamburg Advanced Research Center for Bioorganic Chemistry (HARBOR) & Department of Chemistry, Institute for Biochemistry and Molecular Biology, University of Hamburg, Germany MRC Laboratory of Molecular Biology, Cambridge, United Kingdom Department of Biochemistry and Molecular Cell Biology, University Medical Centre Hamburg-Eppendorf, Germany Export Date: 10 September 2021 CODEN: FJEOA Correspondence Address: Tidow, H.; The Hamburg Advanced Research Center for Bioorganic Chemistry (HARBOR) & Department of Chemistry, Germany; email: tidow@chemie.uni-hamburg.de Funding details: SFB1328 Funding details: Deutsche Forschungsgemeinschaft, DFG, EXC 1074 Funding text 1: We thank members of the Fliegert and Tidow laboratories for helpful discussions. The synchrotron SAXS data were collected at beamline P12 operated by EMBL Hamburg at the PETRA III storage ring (DESY, Hamburg, Germany). We acknowledge access to the Sample Preparation and Characterization (SPC) Facility of EMBL (Hamburg). This research was funded by the Collaborative Research Centre SFB1328 and the excellence cluster ‘The Hamburg Centre for Ultrafast Imaging ‐ Structure, Dynamics and Control of Matter at the Atomic Scale’ of the Deutsche Forschungsgemeinschaft (DFG EXC 1074). The Hamburg Advanced Research Center for Bioorganic Chemistry (HARBOR) & Department of Chemistry, Institute for Biochemistry and Molecular Biology, University of Hamburg, Germany MRC Laboratory of Molecular Biology, Cambridge, United Kingdom Department of Biochemistry and Molecular Cell Biology, University Medical Centre Hamburg-Eppendorf, Germany Export Date: 13 September 2021 CODEN: FJEOA Correspondence Address: Tidow, H.; The Hamburg Advanced Research Center for Bioorganic Chemistry (HARBOR) & Department of Chemistry, Germany; email: tidow@chemie.uni-hamburg.de Funding details: SFB1328 Funding details: Deutsche Forschungsgemeinschaft, DFG, EXC 1074 Funding text 1: We thank members of the Fliegert and Tidow laboratories for helpful discussions. The synchrotron SAXS data were collected at beamline P12 operated by EMBL Hamburg at the PETRA III storage ring (DESY, Hamburg, Germany). We acknowledge access to the Sample Preparation and Characterization (SPC) Facility of EMBL (Hamburg). This research was funded by the Collaborative Research Centre SFB1328 and the excellence cluster ‘The Hamburg Centre for Ultrafast Imaging ‐ Structure, Dynamics and Control of Matter at the Atomic Scale’ of the Deutsche Forschungsgemeinschaft (DFG EXC 1074). AB - Nudix hydrolase 9 (NUDT9) is a member of the nucleoside linked to another moiety X (NUDIX) protein superfamily, which hydrolyses a broad spectrum of organic pyrophosphates from metabolic processes. ADP-ribose (ADPR) has been the only known endogenous substrate accepted by NUDT9 so far. The Ca2+-permeable transient receptor potential melastatin subfamily 2 (TRPM2) channel contains a homologous NUDT9-homology (NUDT9H) domain and is activated by ADPR. Sustained Ca2+ influx via ADPR-activated TRPM2 triggers apoptotic mechanisms. Thus, a precise regulation of cellular ADPR levels by NUDT9 is essential. A detailed characterization of the enzyme-substrate interaction would help to understand the high substrate specificity of NUDT9. Here, we analysed ligand binding to NUDT9 using a variety of biophysical techniques. We identified 2′-deoxy-ADPR as an additional substrate for NUDT9. Similar enzyme kinetics and binding affinities were determined for the two ligands. The high-affinity binding was preserved in NUDT9 containing the mutated NUDIX box derived from the human NUDT9H domain. NMR spectroscopy indicated that ADPR and 2′-deoxy-ADPR bind to the same binding site of NUDT9. Backbone resonance assignment and subsequent molecular docking allowed further characterization of the binding pocket. Substantial conformational changes of NUDT9 upon ligand binding were observed which might allow for the development of NUDT9-based ADPR fluorescence resonance energy transfer sensors that may help with the analysis of ADPR signalling processes in cells in the future. © 2021 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies LA - English DB - MTMT ER - TY - JOUR AU - Poltronieri, P. AU - Mezzolla, V. AU - Farooqi, A.A. AU - Di, Girolamo M. TI - Nad precursors, mitochondria targeting compounds and adp-ribo-sylation inhibitors in treatment of inflammatory diseases and cancer JF - CURRENT MEDICINAL CHEMISTRY J2 - CURR MED CHEM VL - 28 PY - 2021 IS - 41 SP - 8453 EP - 8479 PG - 27 SN - 0929-8673 DO - 10.2174/0929867328666210118152653 UR - https://m2.mtmt.hu/api/publication/32676975 ID - 32676975 N1 - Cited By :2 Export Date: 15 February 2022 CODEN: CMCHE Correspondence Address: Poltronieri, P.; Institute of Sciences of Food Productions, via Mon-teroni km 7, Italy; email: palmiro.poltronieri@ispa.cnr.it LA - English DB - MTMT ER - TY - JOUR AU - Szöllősi, András TI - Two decades of evolution of our understanding of the transient receptor potential melastatin 2 (Trpm2) cation channel JF - LIFE-BASEL J2 - LIFE-BASEL VL - 11 PY - 2021 IS - 5 PG - 23 SN - 2075-1729 DO - 10.3390/life11050397 UR - https://m2.mtmt.hu/api/publication/32040119 ID - 32040119 N1 - Department of Medical Biochemistry, Semmelweis University, Budapest, 1085, Hungary MTA-SE Lendület Ion Channel Research Group, Semmelweis University, Budapest, 1085, Hungary HCEMM-SE Molecular Channelopathies Research Group, Semmelweis University, Budapest, 1085, Hungary Cited By :2 Export Date: 9 March 2022 Correspondence Address: Szollosi, A.; Department of Medical Biochemistry, Hungary; email: szollosi.andras@med.semmelweis-univ.hu Funding details: 739593 Funding details: LP2017-14/2017 Funding text 1: Supported by MTA Lend?let grant LP2017-14/2017 and EU Horizon 2020 Research and Innovation Program grant 739593. Funding text 2: Funding: Supported by MTA Lendület grant LP2017-14/2017 and EU Horizon 2020 Research and Innovation Program grant 739593. AB - The transient receptor potential melastatin (TRPM) family belongs to the superfamily of TRP ion channels. It consists of eight family members that are involved in a plethora of cellular functions. TRPM2 is a homotetrameric Ca2+-permeable cation channel activated upon oxidative stress and is important, among others, for body heat control, immune cell activation and insulin secretion. Invertebrate TRPM2 proteins are channel enzymes; they hydrolyze the activating ligand, ADP-ribose, which is likely important for functional regulation. Since its cloning in 1998, the understanding of the biophysical properties of the channel has greatly advanced due to a vast number of structure– function studies. The physiological regulators of the channel have been identified and characterized in cell-free systems. In the wake of the recent structural biochemistry revolution, several TRPM2 cryo-EM structures have been published. These structures have helped to understand the general features of the channel, but at the same time have revealed unexplained mechanistic differences among channel orthologues. The present review aims at depicting the major research lines in TRPM2 structure-function. It discusses biophysical properties of the pore and the mode of action of direct channel effectors, and interprets these functional properties on the basis of recent three-dimensional structural models. © 2021 by the author. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - JOUR AU - Zielińska, W. AU - Zabrzyński, J. AU - Gagat, M. AU - Grzanka, A. TI - The role of trpm2 in endothelial function and dysfunction JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 22 PY - 2021 IS - 14 SN - 1661-6596 DO - 10.3390/ijms22147635 UR - https://m2.mtmt.hu/api/publication/32188278 ID - 32188278 N1 - Department of Histology and Embryology, Faculty of Medicine, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Toruń, Bydgoszcz, 85‐092, Poland Department of General Orthopaedics, Musculoskeletal Oncology and Trauma Surgery, University of Medical Sciences, Poznan, 61‐701, Poland Export Date: 10 September 2021 Correspondence Address: Gagat, M.; Department of Histology and Embryology, Poland; email: mgagat@cm.umk.pl Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium, 7440-70-2, 14092-94-5; inorganic pyrophosphatase, 9024-82-2, 9033-44-7; Adenosine Diphosphate Ribose; Calcium; NUDT9; Pyrophosphatases; Reactive Oxygen Species; TRPM Cation Channels; TRPM2 protein, human Funding text 1: The present study was supported by research tasks within the framework of statutory activities no. WL176 (Nicolaus Copernicus University in Toru?, Faculty of Medicine, Collegium Medicum in Bydgoszcz). Funding text 2: Funding: The present study was supported by research tasks within the framework of statutory activities no. WL176 (Nicolaus Copernicus University in Toruń, Faculty of Medicine, Collegium Medicum in Bydgoszcz). AB - The transient receptor potential (TRP) melastatin‐like subfamily member 2 (TRPM2) is a non‐selective calcium‐permeable cation channel. It is expressed by many mammalian tissues, including bone marrow, spleen, lungs, heart, liver, neutrophils, and endothelial cells. The best‐known mechanism of TRPM2 activation is related to the binding of ADP‐ribose to the nudix‐box sequence motif (NUDT9‐H) in the C‐terminal domain of the channel. In cells, the production of ADP‐ribose is a result of increased oxidative stress. In the context of endothelial function, TRPM2‐dependent calcium influx seems to be particularly interesting as it participates in the regulation of barrier function, cell death, cell migration, and angiogenesis. Any impairments of these functions may result in endothelial dysfunction observed in such conditions as atherosclerosis or hypertension. Thus, TRPM2 seems to be an attractive therapeutic target for the conditions connected with the increased production of reactive oxygen species. However, before the application of TRPM2 inhibitors will be possible, some issues need to be resolved. The main issues are the lack of specificity, poor membrane permeabilization, and low stability in in vivo conditions. The article aims to summarize the latest findings on a role of TRPM2 in endothelial cells. We also show some future perspectives for the application of TRPM2 inhibitors in cardiovascular system diseases. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - JOUR AU - Baszczyňski, O. AU - Watt, J.M. AU - Rozewitz, M.D. AU - Fliegert, R. AU - Guse, A.H. AU - Potter, B.V.L. TI - Synthesis of phosphonoacetate analogues of the second messenger adenosine 5′-diphosphate ribose (ADPR) JF - RSC ADVANCES J2 - RSC ADV VL - 10 PY - 2020 IS - 3 SP - 1776 EP - 1785 PG - 10 SN - 2046-2069 DO - 10.1039/c9ra09284f UR - https://m2.mtmt.hu/api/publication/31258315 ID - 31258315 N1 - Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Export Date: 24 March 2020 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, SFB1328, 335447717 Funding details: Wellcome Trust, WT Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Export Date: 26 March 2020 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, SFB1328, 335447717 Funding details: Wellcome Trust, WT Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Export Date: 3 July 2020 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, SFB1328, 335447717 Funding details: Wellcome Trust, WT Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Export Date: 14 July 2020 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, SFB1328, 335447717 Funding details: Wellcome Trust, WT Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Cited By :3 Export Date: 9 December 2020 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, SFB1328, 335447717 Funding details: Wellcome Trust, WT Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Bath, BA2 7AY, United Kingdom Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center, Hamburg-Eppendorf Martinistrasse 52, Hamburg, 20246, Germany Cited By :3 Export Date: 9 April 2021 CODEN: RSCAC Correspondence Address: Potter, B.V.L.; Medicinal Chemistry and Drug Discovery, Mansfield Road, United Kingdom; email: barry.potter@pharm.ox.ac.uk Funding details: Wellcome Trust, WT Funding details: European Commission, EU, DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, 335447717, SFB1328 Funding text 1: This work was supported by the Deutsche For-schungsgemeinscha (DFG) (Project number 335447717; SFB1328, project A01 to A. H. G, SFB1328, project A05 to R. F) and the Wellcome Trust. BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Research in the Guse/Fliegert labs is also supported by the Joachim-Herz-Foundation, Infecto-physics consortium, project 4; and EU project INTEGRATA - DLV-813284. AB - Adenosine 5′-diphosphate ribose (ADPR) is an intracellular signalling molecule generated from nicotinamide adenine dinucleotide (NAD+). Synthetic ADPR analogues can shed light on the mechanism of activation of ADPR targets and their downstream effects. Such chemical biology studies, however, are often challenging due to the negatively charged pyrophosphate that is also sensitive to cellular pyrophosphatases. Prior work on an initial ADPR target, the transient receptor potential cation channel TRPM2, showed complete pyrophosphate group replacement to be a step too far in maintaining biological activity. Thus, we designed ADPR analogues with just one of the negatively charged phosphate groups removed, by employing a phosphonoacetate linker. Synthesis of two novel phosphonoacetate ADPR analogues is described via tandem N,N′-dicyclohexylcarbodiimide coupling to phosphonoacetic acid. Neither analogue, however, showed significant agonist or antagonist activity towards TRPM2, underlining the importance of a complete pyrophosphate motif in activation of this particular receptor. © 2019 The Royal Society of Chemistry. LA - English DB - MTMT ER - TY - JOUR AU - Cruz-Torres, I. AU - Backos, D.S. AU - Herson, P.S. TI - Characterization and optimization of the novel transient receptor potential melastatin 2 antagonist TaTM2Nx JF - MOLECULAR PHARMACOLOGY J2 - MOL PHARMACOL VL - 97 PY - 2020 IS - 2 SP - 102 EP - 111 PG - 10 SN - 0026-895X DO - 10.1124/mol.119.117549 UR - https://m2.mtmt.hu/api/publication/31368948 ID - 31368948 N1 - Departments of Pharmacology, United States Anesthesiology, United States Neuronal Injury and Plasticity Program, University of Colorado School of Medicine, Aurora, CO, United States Department of Pharmaceutical Sciences, University of Colorado Skaggs, School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, United States Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, Aurora, CO 80045, United States Export Date: 3 July 2020 CODEN: MOPMA Correspondence Address: Cruz-Torres, I.; Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, United States; email: ivelisse.cruz-torres@ucdenver.edu Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; Peptides; tat Gene Products, Human Immunodeficiency Virus; TRPM Cation Channels; TRPM2 protein, human Funding details: National Institutes of Health, NIH, T32GM007635, R01NS092645 Funding text 1: This work was supported by the National Institutes of Health Grant T32GM007635 (Pharmacology Training Grant) and Grant R01NS092645 (to P.S.H.). https://doi.org/10.1124/mol.119.117549. s This article has supplemental material available at molpharm.aspetjournals. org. Departments of Pharmacology, United States Anesthesiology, United States Neuronal Injury and Plasticity Program, University of Colorado School of Medicine, Aurora, CO, United States Department of Pharmaceutical Sciences, University of Colorado Skaggs, School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, United States Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, Aurora, CO 80045, United States Export Date: 14 July 2020 CODEN: MOPMA Correspondence Address: Cruz-Torres, I.; Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, United States; email: ivelisse.cruz-torres@ucdenver.edu Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; Peptides; tat Gene Products, Human Immunodeficiency Virus; TRPM Cation Channels; TRPM2 protein, human Funding details: National Institutes of Health, NIH, T32GM007635, R01NS092645 Funding text 1: This work was supported by the National Institutes of Health Grant T32GM007635 (Pharmacology Training Grant) and Grant R01NS092645 (to P.S.H.). https://doi.org/10.1124/mol.119.117549. s This article has supplemental material available at molpharm.aspetjournals. org. Departments of Pharmacology, United States Anesthesiology, United States Neuronal Injury and Plasticity Program, University of Colorado School of Medicine, Aurora, CO, United States Department of Pharmaceutical Sciences, University of Colorado Skaggs, School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, United States Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, Aurora, CO 80045, United States Cited By :1 Export Date: 9 December 2020 CODEN: MOPMA Correspondence Address: Cruz-Torres, I.; Department of Anesthesiology, University of Colorado School of Medicine, 12800 E. 19th Ave, United States; email: ivelisse.cruz-torres@ucdenver.edu Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; Peptides; tat Gene Products, Human Immunodeficiency Virus; TRPM Cation Channels; TRPM2 protein, human Funding details: National Institutes of Health, NIH, T32GM007635, R01NS092645 Funding text 1: This work was supported by the National Institutes of Health Grant T32GM007635 (Pharmacology Training Grant) and Grant R01NS092645 (to P.S.H.). https://doi.org/10.1124/mol.119.117549. s This article has supplemental material available at molpharm.aspetjournals. org. AB - Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable channel activated by adenosine diphosphate ribose metabolites and oxidative stress. TRPM2 contributes to neuronal injury in the brain caused by stroke and cardiac arrest among other diseases including pain, inflammation, and cancer. However, the lack of specific inhibitors hinders the study of TRPM2 in brain pathophysiology. Here, we present the design of a novel TRPM2 antagonist, tatM2NX, which prevents ligand binding and TRPM2 activation. We used mutagenesis of tatM2NX to determine the structure-activity relationship and antagonistic mechanism on TRPM2 using whole-cell patch clamp and Calcium imaging in human embryonic kidney 293 cells with stable human TRPM2 expression. We show that tatM2NX inhibits over 90% of TRPM2 channel currents at concentrations as low as 2 mM. Moreover, tatM2NX is a potent antagonist with an IC50 of 396 nM. Our results from tatM2NX mutagenesis indicate that specific residues within the tatM2NX C terminus are required to confer antagonism on TRPM2. Therefore, the peptide tatM2NX represents a new tool for the study of TRPM2 function in cell biology and enhances our understanding of TRPM2 in disease. SIGNIFICANCE STATEMENT TatM2NX is a potent TRPM2 channel antagonist with the potential for clinical benefit in neurological diseases. This study characterizes interactions of tatM2NX with TRPM2 and the mechanism of action using structure-activity analysis. © 2020 by The American Society for Pharmacology and Experimental Therapeutics LA - English DB - MTMT ER - TY - CHAP AU - Galione, A. AU - Chuang, K.-T. TI - Pyridine Nucleotide Metabolites and Calcium Release from Intracellular Stores T2 - Calcium Signaling (2nd edition) VL - 1131 PB - Springer Netherlands CY - New York, New York T3 - Advances in Experimental Medicine and Biology, ISSN 0065-2598 ; 1131. PY - 2020 SP - 371 EP - 394 PG - 24 DO - 10.1007/978-3-030-12457-1_15 UR - https://m2.mtmt.hu/api/publication/31042546 ID - 31042546 N1 - Export Date: 7 January 2020 CODEN: AEMBA Correspondence Address: Galione, A.; Department of Pharmacology, University of OxfordUnited Kingdom; email: antony.galione@pharm.ox.ac.uk Export Date: 8 January 2020 CODEN: AEMBA Correspondence Address: Galione, A.; Department of Pharmacology, University of OxfordUnited Kingdom; email: antony.galione@pharm.ox.ac.uk Cited By :1 Export Date: 3 July 2020 CODEN: AEMBA Correspondence Address: Galione, A.; Department of Pharmacology, University of OxfordUnited Kingdom; email: antony.galione@pharm.ox.ac.uk Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; nicotinic acid, 54-86-4, 59-67-6; nicotinic acid adenine dinucleotide phosphate, 5502-96-5; calcium, 7440-70-2, 14092-94-5; cyclic adenosine diphosphate ribose, 119340-53-3; nicotinamide adenine dinucleotide phosphate, 53-59-8; Calcium; Cyclic ADP-Ribose; NADP; Pyridines; Ryanodine Receptor Calcium Release Channel Cited By :1 Export Date: 9 December 2020 CODEN: AEMBA Correspondence Address: Galione, A.; Department of Pharmacology, University of OxfordUnited Kingdom; email: antony.galione@pharm.ox.ac.uk Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; nicotinic acid, 54-86-4, 59-67-6; nicotinic acid adenine dinucleotide phosphate, 5502-96-5; calcium, 7440-70-2, 14092-94-5; cyclic adenosine diphosphate ribose, 119340-53-3; nicotinamide adenine dinucleotide phosphate, 53-59-8; Calcium; Cyclic ADP-Ribose; NADP; Pyridines; Ryanodine Receptor Calcium Release Channel LA - English DB - MTMT ER - TY - JOUR AU - Huang, Yihe AU - Fliegert, Ralf AU - Guse, Andreas H. AU - Lu, Wei AU - Du, Juan TI - A structural overview of the ion channels of the TRPM family JF - CELL CALCIUM J2 - CELL CALCIUM VL - 85 PY - 2020 PG - 11 SN - 0143-4160 DO - 10.1016/j.ceca.2019.102111 UR - https://m2.mtmt.hu/api/publication/31042507 ID - 31042507 N1 - Funding Agency and Grant Number: McKnight Scholar Award; Klingenstein-Simon Scholar Award; National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01NS111031-01]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R56HL144929-01]; Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation)German Research Foundation (DFG) [335447727 -SFB 1328, INTEGRATA -DLV-813284] Funding text: We thank D. Nadziejka for technical editing. We appreciate Du and Lu lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award, and a National Institutes of Health (NIH) grant (1R01NS111031-01). W.L. is supported by a NIH grant (1R56HL144929-01). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) -Project-ID: 335447727 -SFB 1328 (Joachim-Herz-Foundation, Infectophysics consortium, project 4; and EU project INTEGRATA -DLV-813284). Export Date: 7 January 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Export Date: 8 January 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Export Date: 14 February 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :6 Export Date: 1 July 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :6 Export Date: 3 July 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :6 Export Date: 14 July 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :6 Export Date: 20 July 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :18 Export Date: 9 December 2020 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: McKnight Foundation Funding details: National Institutes of Health, NIH, 1R56HL144929-01, 1R01NS111031-01 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Van Andel Institute, 333 Bostwick Ave., N.E., Grand Rapids, MI 49503, United States The Calcium Signaling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, Hamburg, D-20246, Germany Cited By :27 Export Date: 9 April 2021 CODEN: CECAD Correspondence Address: Lü, W.; Van Andel Institute, 333 Bostwick Ave., N.E., United States; email: wei.lu@vai.org Funding details: National Institutes of Health, NIH, 1R01NS111031-01, 1R56HL144929-01 Funding details: McKnight Foundation Funding details: European Commission, EU, INTEGRATA - DLV-813284 Funding details: Deutsche Forschungsgemeinschaft, DFG, 335447727 - SFB 1328 Funding details: German-Israeli Foundation for Scientific Research and Development, GIF, SFB 1328 Funding text 1: We thank D. Nadziejka for technical editing. We appreciate Du and Lü lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award , and a National Institutes of Health (NIH) grant ( 1R01NS111031-01 ). W.L. is supported by a NIH grant ( 1R56HL144929-01 ). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 ( Joachim-Herz-Foundation , Infectophysics consortium, project 4 ; and EU project INTEGRATA - DLV-813284 ). Funding text 2: We thank D. Nadziejka for technical editing. We appreciate Du and L? lab members including T. Walter, E. Haley, and Z. Ruan for proofreading. J.D. is supported by a McKnight Scholar Award, a Klingenstein-Simon Scholar Award, and a National Institutes of Health (NIH) grant (1R01NS111031-01). W.L. is supported by a NIH grant (1R56HL144929-01). Research in the Guse/Fliegert labs is supported by Deutsche Forschungs-gemeinschaft (DFG, German Research Foundation) - Project-ID: 335447727 - SFB 1328 (Joachim-Herz-Foundation, Infectophysics consortium, project 4; and EU project INTEGRATA - DLV-813284). AB - The TRPM (transient receptor potential melastatin) family belongs to the superfamily of TRP cation channels. The TRPM subfamily is composed of eight members that are involved in diverse biological functions such as temperature sensing, inflammation, insulin secretion, and redox sensing. Since the first cloning of TRPM1 in 1998, tremendous progress has been made uncovering the function, structure, and pharmacology of this family. Complete structures of TRPM2, TRPM4, and TRPM8, as well as a partial structure of TRPM7, have been determined by cryo-EM, providing insights into their channel assembly, ion permeation, gating mechanisms, and structural pharmacology. Here we summarize the current knowledge about channel structure, emphasizing general features and principles of the structure of TRPM channels discovered since 2017. We also discuss some of the key unresolved issues in the field, including the molecular mechanisms underlying voltage and temperature dependence, as well as the functions of the TRPM channels' C-terminal domains. LA - English DB - MTMT ER - TY - JOUR AU - Islam, Md Shahidul TI - Molecular Regulations and Functions of the Transient Receptor Potential Channels of the Islets of Langerhans and Insulinoma Cells JF - CELLS J2 - CELLS-BASEL VL - 9 PY - 2020 IS - 3 PG - 22 SN - 2073-4409 DO - 10.3390/cells9030685 UR - https://m2.mtmt.hu/api/publication/31427816 ID - 31427816 AB - Insulin secretion from the beta-cells of the islets of Langerhans is triggered mainly by nutrients such as glucose, and incretin hormones such as glucagon-like peptide-1 (GLP-1). The mechanisms of the stimulus-secretion coupling involve the participation of the key enzymes that metabolize the nutrients, and numerous ion channels that mediate the electrical activity. Several members of the transient receptor potential (TRP) channels participate in the processes that mediate the electrical activities and Ca2+ oscillations in these cells. Human beta-cells express TRPC1, TRPM2, TRPM3, TRPM4, TRPM7, TRPP1, TRPML1, and TRPML3 channels. Some of these channels have been reported to mediate background depolarizing currents, store-operated Ca2+ entry (SOCE), electrical activity, Ca2+ oscillations, gene transcription, cell-death, and insulin secretion in response to stimulation by glucose and GLP1. Different channels of the TRP family are regulated by one or more of the following mechanisms: activation of G protein-coupled receptors, the filling state of the endoplasmic reticulum Ca2+ store, heat, oxidative stress, or some second messengers. This review briefly compiles our current knowledge about the molecular mechanisms of regulations, and functions of the TRP channels in the beta-cells, the alpha-cells, and some insulinoma cell lines. LA - English DB - MTMT ER - TY - JOUR AU - Kuehn, Frank J. P. TI - Structure-Function Relationship of TRPM2: Recent Advances, Contradictions, and Open Questions JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 21 PY - 2020 IS - 18 PG - 16 SN - 1661-6596 DO - 10.3390/ijms21186481 UR - https://m2.mtmt.hu/api/publication/31697231 ID - 31697231 N1 - Export Date: 9 December 2020 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, University Hospital RWTH AachenGermany; email: fkuehn@ukaachen.de Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). Export Date: 7 April 2021 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Germany; email: fkuehn@ukaachen.de Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). Export Date: 9 April 2021 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Germany; email: fkuehn@ukaachen.de Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). Export Date: 12 April 2021 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Germany; email: fkuehn@ukaachen.de Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; Calcium; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). Cited By :5 Export Date: 9 September 2021 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Germany; email: fkuehn@ukaachen.de Chemicals/CAS: adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; hemagglutinin, 37333-12-3; serine, 56-45-1, 6898-95-9; calcium, 7440-70-2, 14092-94-5; Calcium; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). Cited By :5 Export Date: 15 September 2021 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Germany; email: fkuehn@ukaachen.de Chemicals/CAS: adenosine triphosphate, 15237-44-2, 56-65-5, 987-65-5; hemagglutinin, 37333-12-3; serine, 56-45-1, 6898-95-9; calcium, 7440-70-2, 14092-94-5; Calcium; TRPM Cation Channels; TRPM2 protein, human Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: Funding: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). AB - When in a particular scientific field, major progress is rapidly reached after a long period of relative stand-still, this is often achieved by the development or exploitation of new techniques and methods. A striking example is the new insights brought into the understanding of the gating mechanism of the transient receptor potential melastatin type 2 cation channel (TRPM2) by cryogenic electron microscopy structure analysis. When conventional methods are complemented by new ones, it is quite natural that established researchers are not fully familiar with the possibilities and limitations of the new method. On the other hand, newcomers may need some assistance in perceiving the previous knowledge in detail; they may not realize that some of their interpretations are at odds with previous results and need refinement. This may in turn trigger further studies with new and promising perspectives, combining the promises of several methodological approaches. With this review, I aim to give a comprehensive overview on functional data of several orthologous of TRPM2 that are nicely explained by structural studies. Moreover, I wish to point out some functional contradictions raised by the structural data. Finally, some open questions and some lines of possible future experimental approaches shall be discussed. LA - English DB - MTMT ER - TY - JOUR AU - Malko, P. AU - Jiang, L.-H. TI - TRPM2 channel-mediated cell death: An important mechanism linking oxidative stress-inducing pathological factors to associated pathological conditions JF - REDOX BIOLOGY J2 - REDOX BIOL VL - 37 PY - 2020 PG - 20 SN - 2213-2317 DO - 10.1016/j.redox.2020.101755 UR - https://m2.mtmt.hu/api/publication/31731758 ID - 31731758 N1 - Cited By :25 Export Date: 12 December 2022 Correspondence Address: Jiang, L.-H.; School of Biomedical Science, United Kingdom; email: l.h.jiang@leeds.ac.uk AB - Oxidative stress resulting from the accumulation of high levels of reactive oxygen species is a salient feature of, and a well-recognised pathological factor for, diverse pathologies. One common mechanism for oxidative stress damage is via the disruption of intracellular ion homeostasis to induce cell death. TRPM2 is a non-selective Ca2+-permeable cation channel with a wide distribution throughout the body and is highly sensitive to activation by oxidative stress. Recent studies have collected abundant evidence to show its important role in mediating cell death induced by miscellaneous oxidative stress-inducing pathological factors, both endogenous and exogenous, including ischemia/reperfusion and the neurotoxicants amyloid-β peptides and MPTP/MPP+ that cause neuronal demise in the brain, myocardial ischemia/reperfusion, proinflammatory mediators that disrupt endothelial function, diabetogenic agent streptozotocin and diabetes risk factor free fatty acids that induce loss of pancreatic β-cells, bile acids that damage pancreatic acinar cells, renal ischemia/reperfusion and albuminuria that are detrimental to kidney cells, acetaminophen that triggers hepatocyte death, and nanoparticles that injure pericytes. Studies have also shed light on the signalling mechanisms by which these pathological factors activate the TRPM2 channel to alter intracellular ion homeostasis leading to aberrant initiation of various cell death pathways. TRPM2-mediated cell death thus emerges as an important mechanism in the pathogenesis of conditions including ischemic stroke, neurodegenerative diseases, cardiovascular diseases, diabetes, pancreatitis, chronic kidney disease, liver damage and neurovascular injury. These findings raise the exciting perspective of targeting the TRPM2 channel as a novel therapeutic strategy to treat such oxidative stress-associated diseases. © 2020 The Author(s) LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Balázs AU - Iordanov, Iordan AU - Csanády, László TI - Selective profiling of N- And C-terminal nucleotide-binding sites in a TRPM2 channel JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 152 PY - 2020 IS - 5 PG - 13 SN - 0022-1295 DO - 10.1085/jgp.201912533 UR - https://m2.mtmt.hu/api/publication/31365406 ID - 31365406 N1 - Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary MTA-SE Lendület Ion Channel Research Group, Semmelweis University, Budapest, Hungary Cited By :7 Export Date: 15 September 2021 CODEN: JGPLA Correspondence Address: Tóth, B.; Department of Medical Biochemistry, Hungary; email: toth.balazs@med.semmelweis-univ.hu Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; amino acid, 65072-01-7; calcium, 7440-70-2, 14092-94-5; Adenosine Diphosphate Ribose; Amino Acids; Calcium; Ligands; Nucleotides; TRPM Cation Channels; TRPM2 protein, human Funding details: Semmelweis Egyetem, 18-4-SE-132, 19-4-SE-49 Funding details: Magyar Tudományos Akadémia, MTA, LP2017-14/2017 Funding text 1: Supported by the Hungarian Academy of Sciences (Lendület grant LP2017-14/2017 to L. Csanády) and a Ministry of Human Capacities of Hungary New National Excellence Program (Új Nemzeti Kiválóság Program) award to Semmelweis University. B. Tóth is a János Bolyai Research Fellow, supported by postdoctoral Új Nemzeti Kiválóság Program grants 18-4-SE-132 and 19-4-SE-49. The authors declare no competing financial interests. AB - Transient receptor potential melastatin 2 (TRPM2) is a homotetrameric Ca2+-permeable cation channel important for the immune response, body temperature regulation, and insulin secretion, and is activated by cytosolic Ca2+ and ADP ribose (ADPR). ADPR binds to two distinct locations, formed by large N- and C-terminal cytosolic domains, respectively, of the channel protein. In invertebrate TRPM2 channels, the C-terminal site is not required for channel activity but acts as an active ADPR phosphohydrolase that cleaves the activating ligand. In vertebrate TRPM2 channels, the C-terminal site is catalytically inactive but cooperates with the N-terminal site in channel activation. The precise functional contributions to channel gating and the nucleotide selectivities of the two sites in various species have not yet been deciphered. For TRPM2 of the sea anemone Nematostella vectensis (nvTRPM2), catalytic activity is solely attributable to the C-terminal site. Here, we show that nvTRPM2 channel gating properties remain unaltered upon deletion of the C-terminal domain, indicating that the N-terminal site is single-handedly responsible for channel gating. Exploiting such functional independence of the N- and C-terminal sites, we selectively measure their affinity profiles for a series of ADPR analogues, as reflected by apparent affinities for channel activation and catalysis, respectively. Using site-directed mutagenesis, we confirm that the same N-terminal site observed in vertebrate TRPM2 channels was already present in ancient cnidarians. Finally, by characterizing the functional effects of six amino acid side chain truncations in the N-terminal site, we provide first insights into the mechanistic contributions of those side chains to TRPM2 channel gating. © 2020 Tóth et al. This article is distributed under the terms of an Attribution-Noncommercial-Share Alike-No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution-Noncommercial-Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). LA - English DB - MTMT ER - TY - JOUR AU - Yu, Peilin AU - Cai, Xiaobo AU - Liang, Yan AU - Wang, Mingxiang AU - Yang, Wei TI - Roles of NAD+ and its metabolites regulated calcium channels in cancer JF - MOLECULES J2 - MOLECULES VL - 25 PY - 2020 IS - 20 PG - 20 SN - 1420-3049 DO - 10.3390/molecules25204826 UR - https://m2.mtmt.hu/api/publication/31647884 ID - 31647884 N1 - Department of Toxicology, Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China BrioPryme Biologics, Inc., Hangzhou, Zhejiang 310058, China CODEN: MOLEF Correspondence Address: Yang, W.; Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn Funding details: Natural Science Foundation of Zhejiang Province, LY19B020013 Funding details: National Natural Science Foundation of China, NSFC, 31872796, 32071102, 81371302 Funding text 1: Funding: This work was supported by the Natural Science Foundation of China (31872796 and 81371302 to W.Y., 32071102 to P.Y.), and Zhejiang Provincial Natural Science Foundation (LY19B020013 to P.Y.). Department of Toxicology, Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China BrioPryme Biologics, Inc., Hangzhou, Zhejiang 310058, China Export Date: 8 December 2020 CODEN: MOLEF Correspondence Address: Yang, W.; Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn Funding details: Natural Science Foundation of Zhejiang Province, LY19B020013 Funding details: National Natural Science Foundation of China, NSFC, 31872796, 32071102, 81371302 Funding text 1: Funding: This work was supported by the Natural Science Foundation of China (31872796 and 81371302 to W.Y., 32071102 to P.Y.), and Zhejiang Provincial Natural Science Foundation (LY19B020013 to P.Y.). Department of Toxicology, Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China BrioPryme Biologics, Inc., Hangzhou, Zhejiang 310058, China Export Date: 9 April 2021 CODEN: MOLEF Correspondence Address: Yang, W.; Department of Biophysics, China; email: yangwei@zju.edu.cn Funding details: National Natural Science Foundation of China, NSFC, 31872796, 32071102, 81371302 Funding details: Natural Science Foundation of Zhejiang Province, LY19B020013 Funding text 1: Funding: This work was supported by the Natural Science Foundation of China (31872796 and 81371302 to W.Y., 32071102 to P.Y.), and Zhejiang Provincial Natural Science Foundation (LY19B020013 to P.Y.). Department of Toxicology, Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China BrioPryme Biologics, Inc., Hangzhou, Zhejiang 310058, China Export Date: 12 April 2021 CODEN: MOLEF Correspondence Address: Yang, W.; Department of Biophysics, China; email: yangwei@zju.edu.cn Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; nicotinamide adenine dinucleotide, 53-84-9; Calcium; Calcium Channels; MCOLN1 protein, human; NAD; Transient Receptor Potential Channels; TRPM Cation Channels; TRPM2 protein, human Funding details: National Natural Science Foundation of China, NSFC, 31872796, 32071102, 81371302 Funding details: Natural Science Foundation of Zhejiang Province, LY19B020013 Funding text 1: Funding: This work was supported by the Natural Science Foundation of China (31872796 and 81371302 to W.Y., 32071102 to P.Y.), and Zhejiang Provincial Natural Science Foundation (LY19B020013 to P.Y.). Department of Toxicology, Department of Medical Oncology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China Department of Biophysics, Department of Neurosurgery of the, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China BrioPryme Biologics, Inc., Hangzhou, Zhejiang 310058, China Cited By :1 Export Date: 9 September 2021 CODEN: MOLEF Correspondence Address: Yang, W.; Department of Biophysics, China; email: yangwei@zju.edu.cn Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; nicotinamide adenine dinucleotide, 53-84-9; Calcium; Calcium Channels; MCOLN1 protein, human; NAD; Transient Receptor Potential Channels; TRPM Cation Channels; TRPM2 protein, human Funding details: National Natural Science Foundation of China, NSFC, 31872796, 32071102, 81371302 Funding details: Natural Science Foundation of Zhejiang Province, LY19B020013 Funding text 1: Funding: This work was supported by the Natural Science Foundation of China (31872796 and 81371302 to W.Y., 32071102 to P.Y.), and Zhejiang Provincial Natural Science Foundation (LY19B020013 to P.Y.). AB - Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for redox enzymes, but also moonlights as a regulator for ion channels, the same as its metabolites. Ca2+ homeostasis is dysregulated in cancer cells and affects processes such as tumorigenesis, angiogenesis, autophagy, progression, and metastasis. Herein, we summarize the regulation of the most common calcium channels (TRPM2, TPCs, RyRs, and TRPML1) by NAD+ and its metabolites, with a particular focus on their roles in cancers. Although the mechanisms of NAD+ metabolites in these pathological processes are yet to be clearly elucidated, these ion channels are emerging as potential candidates of alternative targets for anticancer therapy. © 2020 by the authors. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - JOUR AU - Zhang, H. AU - Zhao, S. AU - Yu, J. AU - Yang, W. AU - Liu, Z. AU - Zhang, L. TI - Medicinal chemistry perspective of TRPM2 channel inhibitors: where we are and where we might be heading? JF - DRUG DISCOVERY TODAY J2 - DRUG DISCOV TODAY VL - 25 PY - 2020 IS - 12 SP - 2326 EP - 2334 PG - 9 SN - 1359-6446 DO - 10.1016/j.drudis.2020.09.039 UR - https://m2.mtmt.hu/api/publication/31721987 ID - 31721987 N1 - State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China Department of Biophysics, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China Export Date: 8 December 2020 CODEN: DDTOF Correspondence Address: Liu, Z.; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityChina; email: zmliu@bjmu.edu.cn Funding details: National Major Science and Technology Projects of China, 2018ZX09711001–004-005 Funding details: National Natural Science Foundation of China, NSFC, NSFC 81673279 Funding text 1: This research work was supported financially by National Natural Science Foundation of China (NSFC 81673279 ) and National Science and Technology Major Projects for ‘Major New Drugs Innovation and Development’ ( 2018ZX09711001–004-005 ). We are very grateful to Tingjun Hou and Peilin Yu for reading this manuscript. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China Department of Biophysics, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China Export Date: 9 December 2020 CODEN: DDTOF Correspondence Address: Liu, Z.; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking UniversityChina; email: zmliu@bjmu.edu.cn Funding details: National Major Science and Technology Projects of China, 2018ZX09711001–004-005 Funding details: National Natural Science Foundation of China, NSFC, NSFC 81673279 Funding text 1: This research work was supported financially by National Natural Science Foundation of China (NSFC 81673279 ) and National Science and Technology Major Projects for ‘Major New Drugs Innovation and Development’ ( 2018ZX09711001–004-005 ). We are very grateful to Tingjun Hou and Peilin Yu for reading this manuscript. AB - Transient receptor potential melastatin 2 (TRPM2) is a Ca2+- permeable nonselective cation channel that is involved in diverse biological functions as a cellular sensor for oxidative stress and temperature. It has been considered a promising therapeutic target for the treatment of ischemia/reperfusion (IR) injury, inflammation, cancer, and neurodegenerative diseases. Development of highly potent and selective TRPM2 inhibitors and validation of their use in relevant disease models will advance drug discovery. In this review, we describe the molecular structures and gating mechanism of the TRPM2 channel, and offer a comprehensive review of advances in the discovery of TRPM2 inhibitors. Furthermore, we analyze the properties of reported TRPM2 inhibitors with an emphasis on how specific inhibitors targeting this channel could be better developed. © 2020 Elsevier Ltd LA - English DB - MTMT ER - TY - JOUR AU - Blair, Nathaniel T AU - Carvacho, Ingrid AU - Chaudhuri, Dipayan AU - Clapham, David E AU - DeCaen, Paul AU - Delling, Markus AU - Doerner, Julia F AU - Fan, Lu AU - Ha, Kotdaji AU - Jordt, Sven E TI - Transient receptor potential channels (version 2019.4) in the IUPHAR/BPS guide to pharmacology database JF - IUPHAR/BPS Guide to Pharmacology CITE J2 - GtoPdb CITE VL - 2019 PY - 2019 IS - 4 SN - 2633-1020 DO - 10.2218/gtopdb/F78/2019.4 UR - https://m2.mtmt.hu/api/publication/31625604 ID - 31625604 LA - English DB - MTMT ER - TY - JOUR AU - Gattkowski, Ellen AU - Johnsen, Anke AU - Bauche, Andreas AU - Moeckl, Franziska AU - Kulow, Frederike AU - Alai, Maria Garcia AU - Rutherford, Trevor J. AU - Fliegert, Ralf AU - Tidow, Henning TI - Novel CaM-binding motif in its NudT9H domain contributes to temperature sensitivity of TRPM2 JF - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH J2 - BBA-MOL CELL RES VL - 1866 PY - 2019 IS - 7 SP - 1162 EP - 1170 PG - 9 SN - 0167-4889 DO - 10.1016/j.bbamcr.2018.12.010 UR - https://m2.mtmt.hu/api/publication/30766413 ID - 30766413 N1 - Export Date: 8 January 2020 CODEN: BAMRD Correspondence Address: Fliegert, R.; Department of Biochemistry and Molecular Cell Biology, University Medical Centre Hamburg-Eppendorf, Martinistrasse 52, Germany; email: r.fliegert@uke.de Funding Agency and Grant Number: excellence cluster 'The Hamburg Centre for Ultrafast Imaging - Structure, Dynamics and Control of Matter at the Atomic Scale' of the Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [DFG EXC 1074]; Collaborative Research Consortium "Adenine nucleotides in immunity and inflammation" [DFG SFB 1328] Funding text: We thank K. Veith for technical assistance and members of the Tidow and Fliegert labs for helpful comments on the manuscript. We thank A, Harneit for her initial work on the expression and purification of the NudT9H domain. We acknowledge access to the Sample Preparation and Characterization (SPC) Facility of EMBL, Hamburg. This research was funded by the excellence cluster 'The Hamburg Centre for Ultrafast Imaging - Structure, Dynamics and Control of Matter at the Atomic Scale' of the Deutsche Forschungsgemeinschaft (DFG EXC 1074) and the Collaborative Research Consortium "Adenine nucleotides in immunity and inflammation" (DFG SFB 1328). AB - TRPM2 is a non-selective, Ca2+-permeable cation channel, which plays a role in cell death but also contributes to diverse immune cell functions. In addition, TRPM2 contributes to the control of body temperature and is involved in perception of non-noxious heat and thermotaxis. TRPM2 is regulated by many factors including Ca2+, ADPR, 2'-deoxy-ADPR, Ca2+-CaM, and temperature. However, the molecular basis for the temperature sensitivity of TRPM2 as well as the interplay between the regulatory factors is still not understood.Here we identify a novel CaM-binding site in the unique NudT9H domain of TRPM2. Using a multipronged biophysical approach we show that binding of Ca2+-CaM to this site occurs upon partial unfolding at temperatures > 35 degrees C and prevents further thermal destabilization. In combination with patch-clamp measurements of full-length TRPM2 our results suggest a role of this CaM-binding site in the temperature sensitivity of TRPM2.This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech LA - English DB - MTMT ER - TY - JOUR AU - Kühn, Frank J P AU - Watt, Joanna M AU - Potter, Barry V L AU - Lückhoff, Andreas TI - Different substrate specificities of the two ADPR binding sites in TRPM2 channels of Nematostella vectensis and the role of IDPR. JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 9 PY - 2019 IS - 1 SN - 2045-2322 DO - 10.1038/s41598-019-41531-4 UR - https://m2.mtmt.hu/api/publication/30628107 ID - 30628107 N1 - Funding Agency and Grant Number: Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [KU 2271/4-2]; [101010] Funding text: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). BVLP is a Wellcome Trust Senior Investigator (Grant 101010). Export Date: 7 January 2020 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Medical Faculty, RWTH AachenGermany; email: fkuehn@ukaachen.de Export Date: 8 January 2020 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Medical Faculty, RWTH AachenGermany; email: fkuehn@ukaachen.de Institute of Physiology, Medical Faculty, RWTH Aachen, Aachen, D52057, Germany Medicinal Chemistry and Drug Discovery, Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, United Kingdom Wolfson Laboratory of Medicinal Chemistry, Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, United Kingdom Cited By :7 Export Date: 1 July 2020 Correspondence Address: Kühn, F.J.P.; Institute of Physiology, Medical Faculty, RWTH AachenGermany; email: fkuehn@ukaachen.de Funding details: Deutsche Forschungsgemeinschaft, DFG, KU 2271/4-2 Funding text 1: The study was supported by the Deutsche Forschungsgemeinschaft (DFG, Grant KU 2271/4-2 to FJPK). BVLP is a Wellcome Trust Senior Investigator (Grant 101010). AB - NvTRPM2 (Nematostella vectensis Transient Receptor Potential Melastatin 2), the species variant of the human apoptosis-related cation channel hTRPM2, is gated by ADP-ribose (ADPR) independently of the C-terminal NUDT9H domain that mediates ADPR-directed gating in hTRPM2. The decisive binding site in NvTRPM2 is likely to be identical with the N-terminal ADPR binding pocket in zebra fish DrTRPM2. Our aim was a characterization of this binding site in NvTRPM2 with respect to its substrate specificity, in comparison to the classical ADPR interaction site within NUDT9H that is highly homologous in hTRPM2 and NvTRPM2, although only in NvTRPM2, catalytic (ADPRase) activity is conserved. With various ADPR analogues, key differences of the two sites were identified. Particularly, two reported antagonists on hTRPM2 were agonists on NvTRPM2. Moreover, IDP-ribose (IDPR) induced currents both in hTRPM2 and NvTRPM2 but not in NvTRPM2 mutants in which NUDT9H was absent. Thus, IDPR acts on NUDT9H rather than N-terminally, revealing a regulatory function of NUDT9H in NvTRPM2 opposed to that in hTRPM2. We propose that IDPR competitively inhibits the ADPRase function of NUDT9H and evokes ADPR accumulation. The findings provide important insights into the structure-function relationship of NvTRPM2 and will allow further characterization of the novel ADPR interaction site. LA - English DB - MTMT ER - TY - JOUR AU - Malko, Philippa AU - Syed Mortadza, Sharifah A AU - McWilliam, Joseph AU - Jiang, Lin-Hua TI - TRPM2 Channel in Microglia as a New Player in Neuroinflammation Associated With a Spectrum of Central Nervous System Pathologies. JF - FRONTIERS IN PHARMACOLOGY J2 - FRONT PHARMACOL VL - 10 PY - 2019 SN - 1663-9812 DO - 10.3389/fphar.2019.00239 UR - https://m2.mtmt.hu/api/publication/30628105 ID - 30628105 N1 - Funding Agency and Grant Number: Wellcome TrustWellcome Trust [072275/Z/03/Z]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31471118]; Alzheimer's Research Trust [ART/PPG2009A/2]; Faculty of Biological Sciences of University of Leeds; Government of Malaysia; Laidlaw Scholarship Funding text: This research was supported in part by the research grants from the Wellcome Trust (072275/Z/03/Z), National Natural Science Foundation of China (31471118), and Alzheimer's Research Trust (ART/PPG2009A/2) (L-HJ), a Ph.D. studentship from the Faculty of Biological Sciences of University of Leeds (PM), a Ph.D. scholarship from the Government of Malaysia (SSM), and a Laidlaw Scholarship (JM). AB - Microglial cells in the central nervous system (CNS) are crucial in maintaining a healthy environment for neurons to function properly. However, aberrant microglial cell activation can lead to excessive generation of neurotoxic proinflammatory mediators and neuroinflammation, which represents a contributing factor in a wide spectrum of CNS pathologies, including ischemic stroke, traumatic brain damage, Alzheimer's disease, Parkinson's disease, multiple sclerosis, psychiatric disorders, autism spectrum disorders, and chronic neuropathic pain. Oxidative stress is a salient and common feature of these conditions and has been strongly implicated in microglial cell activation and neuroinflammation. The transient receptor potential melastatin-related 2 (TRPM2) channel, an oxidative stress-sensitive calcium-permeable cationic channel, is highly expressed in microglial cells. In this review, we examine the recent studies that provide evidence to support an important role for the TRPM2 channel, particularly TRPM2-mediated Ca2+ signaling, in mediating microglial cell activation, generation of proinflammatory mediators and neuroinflammation, which are of relevance to CNS pathologies. These findings lead to a growing interest in the TRPM2 channel, a new player in neuroinflammation, as a novel therapeutic target for CNS diseases. LA - English DB - MTMT ER - TY - JOUR AU - Miller, Barbara A TI - TRPM2 in Cancer. JF - CELL CALCIUM J2 - CELL CALCIUM VL - 80 PY - 2019 SP - 8 EP - 17 PG - 10 SN - 0143-4160 DO - 10.1016/j.ceca.2019.03.002 UR - https://m2.mtmt.hu/api/publication/30673027 ID - 30673027 N1 - Funding Agency and Grant Number: National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01-GM117014]; Hyundai Hope on Wheels Scholar Grant; Four Diamonds Fund of the Pennsylvania State University Funding text: This work was supported in part by the National Institutes of Health Grants R01-GM117014; Hyundai Hope on Wheels Scholar Grant; and the Four Diamonds Fund of the Pennsylvania State University. Export Date: 7 January 2020 CODEN: CECAD Correspondence Address: Miller, B.A.; Departments of Pediatrics, Milton S. Hershey Medical Center, P.O. Box 850, United States; email: bmiller3@pennstatehealth.psu.edu Export Date: 8 January 2020 CODEN: CECAD Correspondence Address: Miller, B.A.; Departments of Pediatrics, Milton S. Hershey Medical Center, P.O. Box 850, United States; email: bmiller3@pennstatehealth.psu.edu AB - The TRP ion channel TRPM2 has an essential function in cell survival and protects the viability of a number of cell types after oxidative stress. It is highly expressed in many cancers including breast, prostate, and pancreatic cancer, melanoma, leukemia, and neuroblastoma, suggesting it promotes cancer cell survival. TRPM2 is activated by production of ADP-ribose (ADPR) following oxidative stress, which binds to the C-terminus of TRPM2, resulting in channel opening. In a number of cancers including neuroblastoma, TRPM2 has been shown to preserve viability and mechanisms have been identified. Activation of TRPM2 results in expression of transcription factors and kinases important in cell proliferation and survival including HIF-1/2α, CREB, nuclear factor (erythroid-derived 2)-related factor-2 (Nrf2), and Pyk2, and Src phosphorylation. Together, HIF-1/2α and CREB regulate expression of genes encoding proteins with roles in mitochondrial function including members of the electron transport complex involved in ATP production. These contribute to lower mitochondrial ROS production while expression of antioxidants regulated by HIF-1/2α, FOXO3a, CREB, and Nrf2 is maintained. CREB is also important in control of expression of key proteins involved in autophagy. When TRPM2-mediated calcium influx is inhibited, mitochondria are dysfunctional, cellular bioenergetics are reduced, production of ROS is increased, and autophagy and DNA repair are impaired, decreasing tumor growth and increasing chemotherapy sensitivity. Inhibition of TRPM2 expression or function results in decreased tumor proliferation and/or viability in many malignancies including breast, gastric, pancreatic, prostate, head and neck cancers, melanoma, neuroblastoma, and T-cell and acute myelogenous leukemia. However, in a small number of malignancies, activation of TRPM2 rather than inhibition has been reported to reduce tumor cell survival. Here, TRPM2-mediated Ca2+ signaling and mechanisms of regulation of cancer cell growth and survival are reviewed and controversies discussed. Evidence suggests that targeting TRPM2 may be a novel therapeutic approach in many cancers. LA - English DB - MTMT ER - TY - JOUR AU - Yin, Ying AU - Wu, Mengyu AU - Hsw, Allen L. AU - Borschel, William F. AU - Borgnia, Mario J. AU - Lander, Gabriel C. AU - Lee, Seok-Yong TI - Visualizing structural transitions of ligand-dependent gating of the TRPM2 channel JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 10 PY - 2019 PG - 14 SN - 2041-1723 DO - 10.1038/s41467-019-11733-5 UR - https://m2.mtmt.hu/api/publication/30789149 ID - 30789149 N1 - Funding Agency and Grant Number: National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R35NS097241, DP2EB020402, R21AR072910]; National Institutes of Health Intramural Research ProgramUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA; US National Institute of Environmental Health SciencesUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Environmental Health Sciences (NIEHS) [ZIC ES103326]; Pew Charitable Trusts; AmgenAmgen; National Science Foundation Graduate Student Research FellowshipNational Science Foundation (NSF); NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [S10OD021634] Funding text: Cryo-EM data for TRPM2DR_Ca2+ were collected at The Scripps Research Institute (TSRI) electron microscopy facility. Cryo-EM data for TRPM2DR_Apo and TRPM2DR_ADPR/Ca2+ were collected at the Duke Shared Materials Instrumentation Facility (SMIF). Preliminary cryo-EM work, including sample screening, was performed at the cryo-EM facility at NIEHS. We thank J.C. Ducom at the TSRI High Performance Computing facility for computational support and B. Anderson for microscope support. We thank L. Zubcevic, A. Bartesaghi, and L. Csanady for providing critical manuscript reading, developing a routine for preprocessing, and preliminary functional studies, respectively. This work was supported by the National Institutes of Health (R35NS097241 to S.-Y.L., DP2EB020402 and R21AR072910 to G.C.L.) and by the National Institutes of Health Intramural Research Program; US National Institute of Environmental Health Sciences (ZIC ES103326 to M.J.B). G.C.L is supported as a Searle Scholar, a Pew Scholar in the Biomedical Sciences, supported by the Pew Charitable Trusts, and by an Amgen Young Investigator award. M.W is supported by a National Science Foundation Graduate Student Research Fellowship. Computational analyses of EM data were performed using shared instrumentation funded by NIH S10OD021634. Export Date: 7 January 2020 Correspondence Address: Lee, S.-Y.; Department of Biochemistry, Duke University School of MedicineUnited States; email: seok-yong.lee@duke.edu Export Date: 8 January 2020 Correspondence Address: Lee, S.-Y.; Department of Biochemistry, Duke University School of MedicineUnited States; email: seok-yong.lee@duke.edu Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, United States Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, United States Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, United States Cited By :1 Export Date: 14 February 2020 Correspondence Address: Lee, S.-Y.; Department of Biochemistry, Duke University School of MedicineUnited States; email: seok-yong.lee@duke.edu Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium, 7440-70-2, 14092-94-5; Adenosine Diphosphate Ribose; Calcium; TRPM Cation Channels Funding details: National Science Foundation, NSF Funding details: S10OD021634 Funding details: National Health Research Institutes, NHRI Funding details: National Institutes of Health, NIH, DP2EB020402, R21AR072910, R35NS097241 Funding details: Amgen Funding details: National Institute of Environmental Health Sciences, NIEHS, ZIC ES103326 Funding details: Pew Charitable Trusts, The Pew Charitable Trusts Funding text 1: Cryo-EM data for TRPM2DR_Ca2+ were collected at The Scripps Research Institute (TSRI) electron microscopy facility. Cryo-EM data for TRPM2DR_Apoand TRPM2DR_ADPR/Ca2+ were collected at the Duke Shared Materials Instrumentation Facility (SMIF). Preliminary cryo-EM work, including sample screening, was performed at the cryo-EM facility at NIEHS. We thank J.C. Ducom at the TSRI High Performance Computing facility for computational support and B. Anderson for microscope support. We thank L. Zubcevic, A. Bartesaghi, and L. Csanady for providing critical manuscript reading, developing a routine for preprocessing, and preliminary functional studies, respectively. This work was supported by the National Institutes of Health (R35NS097241 to S.-Y.L., DP2EB020402 and R21AR072910 to G.C.L.) and by the National Institutes of Health Intramural Research Program; US National Institute of Environmental Health Sciences (ZIC ES103326 to M.J.B). G.C.L is supported as a Searle Scholar, a Pew Scholar in the Biomedical Sciences, supported by the Pew Charitable Trusts, and by an Amgen Young Investigator award. M.W is supported by a National Science Foundation Graduate Student Research Fellowship. Computational analyses of EM data were performed using shared instrumentation funded by NIH S10OD021634. Department of Biochemistry, Duke University School of Medicine, Durham, NC 27710, United States Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, United States Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709, United States Cited By :4 Export Date: 1 July 2020 Correspondence Address: Lee, S.-Y.; Department of Biochemistry, Duke University School of MedicineUnited States; email: seok-yong.lee@duke.edu Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium, 7440-70-2, 14092-94-5; Adenosine Diphosphate Ribose; Calcium; TRPM Cation Channels Funding details: National Science Foundation, NSF Funding details: National Institute of Environmental Health Sciences, NIEHS, ZIC ES103326 Funding details: National Institutes of Health, NIH, DP2EB020402, R21AR072910, R35NS097241 Funding details: National Institutes of Health, NIH, S10OD021634 Funding details: Pew Charitable Trusts Funding text 1: Cryo-EM data for TRPM2DR_Ca2+ were collected at The Scripps Research Institute (TSRI) electron microscopy facility. Cryo-EM data for TRPM2DR_Apoand TRPM2DR_ADPR/Ca2+ were collected at the Duke Shared Materials Instrumentation Facility (SMIF). Preliminary cryo-EM work, including sample screening, was performed at the cryo-EM facility at NIEHS. We thank J.C. Ducom at the TSRI High Performance Computing facility for computational support and B. Anderson for microscope support. We thank L. Zubcevic, A. Bartesaghi, and L. Csanady for providing critical manuscript reading, developing a routine for preprocessing, and preliminary functional studies, respectively. This work was supported by the National Institutes of Health (R35NS097241 to S.-Y.L., DP2EB020402 and R21AR072910 to G.C.L.) and by the National Institutes of Health Intramural Research Program; US National Institute of Environmental Health Sciences (ZIC ES103326 to M.J.B). G.C.L is supported as a Searle Scholar, a Pew Scholar in the Biomedical Sciences, supported by the Pew Charitable Trusts, and by an Amgen Young Investigator award. M.W is supported by a National Science Foundation Graduate Student Research Fellowship. Computational analyses of EM data were performed using shared instrumentation funded by NIH S10OD021634. AB - The transient receptor potential melastatin 2 (TRPM2) channel plays a key role in redox sensation in many cell types. Channel activation requires binding of both ADP-ribose (ADPR) and Ca2+. The recently published TRPM2 structures from Danio rerio in the ligand-free and the ADPR/Ca2+-bound conditions represent the channel in closed and open states, which uncovered substantial tertiary and quaternary conformational rearrangements. However, it is unclear how these rearrangements are achieved within the tetrameric channel during channel gating. Here we report the cryo-electron microscopy structures of Danio rerio TRPM2 in the absence of ligands, in complex with Ca2+ alone, and with both ADPR and Ca2+, resolved to similar to 4.3 angstrom, similar to 3.8 angstrom, and similar to 4.2 angstrom, respectively. In contrast to the published results, our studies capture ligand-bound TRPM2 structures in two-fold symmetric intermediate states, offering a glimpse of the structural transitions that bridge the closed and open conformations. LA - English DB - MTMT ER - TY - JOUR AU - Yu, Peilin AU - Liu, Zhenming AU - Yu, Xiafei AU - Ye, Peiwu AU - Liu, Huan AU - Xue, Xiwen AU - Yang, Lixin AU - Li, Zhongtang AU - Wu, Yang AU - Fang, Cheng AU - Zhao, Yong Juan AU - Yang, Fan AU - Luo, Jian Hong AU - Jiang, Lin-Hua AU - Zhang, Liangren AU - Zhang, Lihe AU - Yang, Wei TI - Direct Gating of the TRPM2 Channel by cADPR via Specific Interactions with the ADPR Binding Pocket JF - CELL REPORTS J2 - CELL REP VL - 27 PY - 2019 IS - 12 SP - 3684 EP - + PG - 16 SN - 2211-1247 DO - 10.1016/j.celrep.2019.05.067 UR - https://m2.mtmt.hu/api/publication/30766408 ID - 30766408 N1 - Funding Agency and Grant Number: Natural Science Foundation of ChinaNational Natural Science Foundation of China [81371302, 81571127, 31872796, 31471118, 21572010, 21772005, 31800990, 81673279, 81573273]; National Basic Research Program of ChinaNational Basic Research Program of China [2014CB910300]; National Major New Drugs Innovation and Development [2018ZX09711001004-005]; Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province [LR16H090001, LY19B020013]; 111 ProjectMinistry of Education, China - 111 Project; non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences [2017PT31038, 2018PT31041]; University of Leeds-Zhejiang University Strategic Collaboration Partnership Programme Funding text: We thank Prof. Jie Zheng for constructive discussion. This work was supported by grants from the Natural Science Foundation of China (81371302, 81571127, 31872796, 31471118, 21572010, 21772005, 31800990, 81673279, and 81573273); the National Basic Research Program of China (2014CB910300); National Major New Drugs Innovation and Development (2018ZX09711001004-005); Zhejiang Provincial Natural Science Foundation (LR16H090001, LY19B020013); the 111 Project; the non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2017PT31038, 2018PT31041); and University of Leeds-Zhejiang University Strategic Collaboration Partnership Programme. Export Date: 7 January 2020 Correspondence Address: Yang, W.; Department of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn Export Date: 8 January 2020 Correspondence Address: Yang, W.; Department of Biophysics, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn AB - cADPR is a well-recognized signaling molecule by modulating the RyRs, but considerable debate exists regarding whether cADPR can bind to and gate the TRPM2 channel, which mediates oxidative stress signaling in diverse physiological and pathological processes. Here, we show that purified cADPR evoked TRPM2 channel currents in both whole-cell and cell-free single-channel recordings and specific binding of cADPR to the purified NUDT9-H domain of TRPM2 by surface plasmon resonance. Furthermore, by combining computational modeling with electrophysiological recordings, we show that the TRPM2 channels carrying point mutations at H1346, T1347, L1379, S1391, E1409, and L1484 possess distinct sensitivity profiles for ADPR and cADPR. These results clearly indicate cADPR is a bona fide activator at the TRPM2 channel and clearly delineate the structural basis for cADPR binding, which not only lead to a better understanding in the gating mechanism of TRPM2 channel but also shed light on a cADPR-induced RyRs-independent Ca2+ signaling mechanism. LA - English DB - MTMT ER - TY - JOUR AU - Bishnoi, M AU - Khare, P AU - Brown, L AU - Panchal, SK TI - Transient receptor potential (TRP) channels: a metabolic TR(i)P to obesity prevention and therapy JF - OBESITY REVIEWS J2 - OBES REV VL - 19 PY - 2018 IS - 9 SP - 1269 EP - 1292 PG - 24 SN - 1467-7881 DO - 10.1111/obr.12703 UR - https://m2.mtmt.hu/api/publication/27696723 ID - 27696723 N1 - Funding Agency and Grant Number: Early and Mid-Career Researcher (EMCR) Fellowship; Advance Queensland Early Career Research Fellowship Funding text: The authors acknowledge Early and Mid-Career Researcher (EMCR) Fellowship by the Indian National Science Academy to Dr Mahendra Bishnoi and an Advance Queensland Early Career Research Fellowship to Dr Sunil K Panchal. Department of Food and Nutritional Biotechnology, National Agri-Food Biotechnology Institute, S.A.S. Nagar (Mohali)Punjab, India Functional Foods Research Group, Institute for Agriculture and the Environment, University of Southern Queensland, Toowoomba, QLD, Australia School of Health and Wellbeing, University of Southern Queensland, Toowoomba, QLD, Australia Cited By :6 Export Date: 13 January 2021 CODEN: ORBEB Correspondence Address: Panchal, S.K.; Functional Foods Research Group, Institute for Agriculture and the Environment, University of Southern QueenslandAustralia; email: Sunil.Panchal@usq.edu.au Department of Food and Nutritional Biotechnology, National Agri-Food Biotechnology Institute, S.A.S. Nagar (Mohali)Punjab, India Functional Foods Research Group, Institute for Agriculture and the Environment, University of Southern Queensland, Toowoomba, QLD, Australia School of Health and Wellbeing, University of Southern Queensland, Toowoomba, QLD, Australia Cited By :10 Export Date: 22 September 2021 CODEN: ORBEB Correspondence Address: Panchal, S.K.; Functional Foods Research Group, Australia; email: Sunil.Panchal@usq.edu.au LA - English DB - MTMT ER - TY - JOUR AU - Hernández-Araiza, I AU - Morales-Lázaro, SL AU - Canul-Sánchez, JA AU - Islas, LD AU - Rosenbaum, T TI - Role of lysophosphatidic acid in ion channel function and disease JF - JOURNAL OF NEUROPHYSIOLOGY J2 - J NEUROPHYSIOL VL - 120 PY - 2018 IS - 3 SP - 1198 EP - 1211 PG - 14 SN - 0022-3077 DO - 10.1152/jn.00226.2018 UR - https://m2.mtmt.hu/api/publication/27689514 ID - 27689514 N1 - Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico Cited By :4 Export Date: 28 August 2019 CODEN: JONEA Correspondence Address: Rosenbaum, T.; Instituto de Fisiología Celular, Univ. Nacional Autónoma de MéxicoMexico; email: trosenba@ifc.unam.mx Chemicals/CAS: vanilloid receptor 1, 363242-41-5 Funding details: Consejo Nacional de Ciencia y Tecnología, CONACYT, 77 Funding details: Consejo Nacional de Ciencia y Tecnología, CONACYT, CB-2014-01-238399 Funding details: University of Illinois at Urbana-Champaign, UIUC Funding text 1: Some figures were produced using Visual Molecular Dynamics (VMD) software. VMD was developed by the Theoretical and Computational Biophysics Group of the Beckman Institute for Advanced Science and Technology at the University of Illinois at Urbana-Champaign. GRANTS This work was supported by Dirección General de Asuntos del Personal Académico (DGAPA)-Programa de Apoyo a Proyectos de Investigación e Inovación Tecnológica (PAPIIT) Grant IN200717, Consejo Nacional de Ciencia y Tecnología (CONACyT) Grant CB-2014-01-238399, and CONACyT Fronteras en la Ciencia Grant 77 to T. Rosenbaum; DGAPA-PAPIIT Grant IA202717 to S. L. Morales-Lázaro; and DGAPA-PAPIIT Grant IN203318 to L. D. Islas. Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico Cited By :4 Export Date: 20 September 2019 CODEN: JONEA Correspondence Address: Rosenbaum, T.; Instituto de Fisiología Celular, Univ. Nacional Autónoma de MéxicoMexico; email: trosenba@ifc.unam.mx Funding Agency and Grant Number: Direccion General de Asuntos del Personal Academico (DGAPA)-Programa de Apoyo a Proyectos de Investigacion e Inovacion Tecnologica (PAPIIT) [IN200717]; Consejo Nacional de Ciencia y Tecnologia (CONACyT)Consejo Nacional de Ciencia y Tecnologia (CONACyT) [CB-2014-01-238399]; CONACyT Fronteras en la Ciencia [77]; DGAPA-PAPIIT Grant [IA202717, IN203318] Funding text: This work was supported by Direccion General de Asuntos del Personal Academico (DGAPA)-Programa de Apoyo a Proyectos de Investigacion e Inovacion Tecnologica (PAPIIT) Grant IN200717, Consejo Nacional de Ciencia y Tecnologia (CONACyT) Grant CB-2014-01-238399, and CONACyT Fronteras en la Ciencia Grant 77 to T. Rosenbaum; DGAPA-PAPIIT Grant IA202717 to S. L. Morales-Lazaro; and DGAPA-PAPIIT Grant IN203318 to L. D. Islas. Export Date: 7 January 2020 CODEN: JONEA Correspondence Address: Rosenbaum, T.; Instituto de Fisiología Celular, Univ. Nacional Autónoma de MéxicoMexico; email: trosenba@ifc.unam.mx Departamento de Neurociencia Cognitiva, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City, Mexico Cited By :6 Export Date: 19 March 2020 CODEN: JONEA Correspondence Address: Rosenbaum, T.; Instituto de Fisiología Celular, Univ. Nacional Autónoma de MéxicoMexico; email: trosenba@ifc.unam.mx LA - English DB - MTMT ER - TY - JOUR AU - Hirschler-Laszkiewicz, Iwona AU - Chen, Shu-jen AU - Bao, Lei AU - Wang, JuFang AU - Zhang, Xue-Qian AU - Shanmughapriya, Santhanam AU - Keefer, Kerry AU - Madesh, Muniswamy AU - Cheung, Joseph Y. AU - Miller, Barbara A. TI - The human ion channel TRPM2 modulates neuroblastoma cell survival and mitochondrial function through Pyk2, CREB, and MCU activation JF - AMERICAN JOURNAL OF PHYSIOLOGY: CELL PHYSIOLOGY J2 - AM J PHYSIOL CELL PH VL - 315 PY - 2018 IS - 4 SP - C571 EP - C586 PG - 16 SN - 0363-6143 DO - 10.1152/ajpcell.00098.2018 UR - https://m2.mtmt.hu/api/publication/30547083 ID - 30547083 N1 - Funding Agency and Grant Number: National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01-GM-117014, R01-DK-108185, RO1-HL-123093, RO1-DK-46778, RO1-HL-137426]; Hyundai Hope on Wheels; Four Diamonds Fund of the Pennsylvania State University Funding text: This work was supported in part by National Institutes of Health Grants R01-GM-117014, R01-DK-108185, RO1-HL-123093, RO1-DK-46778, and RO1-HL-137426; Hyundai Hope on Wheels; and the Four Diamonds Fund of the Pennsylvania State University. Export Date: 7 January 2020 CODEN: AJPCD Correspondence Address: Miller, B.A.; Dept. of Pediatrics, Milton S. Hershey Medical Center, P.O. Box 850, Hershey, United States; email: bmiller3@pennstatehealth.psu.edu AB - Transient receptor potential melastatin channel subfamily member 2 (TRPM2) has an essential function in cell survival and is highly expressed in many cancers. Inhibition of TRPM2 in neuroblastoma by depletion with CRISPR technology or expression of dominant negative TRPM2-S has been shown to significantly reduce cell viability. Here, the role of proline-rich tyrosine kinase 2 (Pyk2) in TRPM2 modulation of neuroblastoma viability was explored. In TRPM2-depleted cells, phosphorylation and expression of Pyk2 and cAMP-responsive element-binding protein (CREB), a downstream target, were significantly reduced after application of the chemotherapeutic agent doxorubicin. Overexpression of wild-type Pyk2 rescued cell viability. Reduction of Pyk2 expression with shRNA decreased cell viability and CREB phosphorylation and expression, demonstrating Pyk2 modulates CREB activation. TRPM2 depletion impaired phosphorylation of Src, an activator of Pyk2, and this may be a mechanism to reduce Pyk2 phosphorylation. TRPM2 inhibition was previously demonstrated to decrease mitochondrial function. Here, CREB, Pyk2, and phosphorylated Src were reduced in mitochondria of TRPM2-depleted cells, consistent with their role in modulating expression and activation of mitochondrial proteins. Phosphorylated Src and phosphorylated and total CREB were reduced in TRPM2-depleted nuclei. Expression and function of mitochondrial calcium uniporter (MCU), a target of phosphorylated Pyk2 and CREB, were significantly reduced. Wild-type TRPM2 but not Ca2(+)-impermeable mutant E960D reconstituted phosphorylation and expression of Pyk2 and CREB in TRPM2-depleted cells exposed to doxorubicin. Results demonstrate that TRPM2 expression protects the viability of neuroblastoma through Src, Pyk2, CREB, and MCU activation, which play key roles in maintaining mitochondrial function and cellular bioenergetics. LA - English DB - MTMT ER - TY - JOUR AU - Jiang, L-H AU - Li, X AU - Syed, Mortadza SA AU - Lovatt, M AU - Yang, W TI - The TRPM2 channel nexus from oxidative damage to Alzheimer's pathologies: An emerging novel intervention target for age-related dementia JF - AGEING RESEARCH REVIEWS J2 - AGEING RES REV VL - 47 PY - 2018 SP - 67 EP - 79 PG - 13 SN - 1568-1637 DO - 10.1016/j.arr.2018.07.002 UR - https://m2.mtmt.hu/api/publication/27692933 ID - 27692933 N1 - Funding Agency and Grant Number: National Natural Science Foundation of ChinaNational Natural Science Foundation of China [31471118]; Department of Education of Henan Province China [16IRTSTHN020]; Wellcome TrustWellcome Trust; Alzheimer's Research Trust; University of Leeds-Zhejiang University; Disciplinary Group of Psychology and Neuroscience Xinxiang Medical University; University of Leeds-Chinese Scholar Council; Malaysian Governmental PhD Scholarship; Royal Society fellowshipRoyal Society of London Funding text: The authors' own works described in this article were supported by grants from National Natural Science Foundation of China (31471118), Department of Education of Henan Province China (16IRTSTHN020), Wellcome Trust, Alzheimer's Research Trust, University of Leeds-Zhejiang University Strategic Collaboration Partnership Programme and Disciplinary Group of Psychology and Neuroscience Xinxiang Medical University (LHJ), and by University of Leeds-Chinese Scholar Council PhD scholarship (XL), Malaysian Governmental PhD Scholarship (SASM) and Royal Society fellowship (WY). Export Date: 7 January 2020 CODEN: ARRGA Correspondence Address: Jiang, L.-H.; School of Biomedical Sciences, Faculty of Biological Sciences, University of LeedsUnited Kingdom; email: l.h.jiang@leeds.ac.uk Export Date: 8 January 2020 CODEN: ARRGA Correspondence Address: Jiang, L.-H.; School of Biomedical Sciences, Faculty of Biological Sciences, University of LeedsUnited Kingdom; email: l.h.jiang@leeds.ac.uk LA - English DB - MTMT ER - TY - JOUR AU - Liu, Xibao AU - Ong, Hwei Ling AU - Ambudkar, Indu TI - TRP Channel Involvement in Salivary Glands-Some Good, Some Bad JF - CELLS J2 - CELLS-BASEL VL - 7 PY - 2018 IS - 7 PG - 18 SN - 2073-4409 DO - 10.3390/cells7070074 UR - https://m2.mtmt.hu/api/publication/27609698 ID - 27609698 N1 - Cited By :21 Export Date: 19 April 2023 Correspondence Address: Ambudkar, I.; Secretory Physiology Section, United States; email: indu.ambudkar@nih.gov LA - English DB - MTMT ER - TY - JOUR AU - Luo, Yuhuan AU - Yu, Xiafei AU - Ma, Cheng AU - Luo, Jianhong AU - Yang, Wei TI - Identification of a Novel EF-Loop in the N-terminus of TRPM2 Channel Involved in Calcium Sensitivity JF - FRONTIERS IN PHARMACOLOGY J2 - FRONT PHARMACOL VL - 9 PY - 2018 PG - 15 SN - 1663-9812 DO - 10.3389/fphar.2018.00581 UR - https://m2.mtmt.hu/api/publication/27589547 ID - 27589547 N1 - Funding Agency and Grant Number: 111 projectMinistry of Education, China - 111 Project; National Natural Science Foundation of ChinaNational Natural Science Foundation of China [81371302, 81571127]; National Basic Research Program of ChinaNational Basic Research Program of China [2013CB910204, 2014CB910300]; Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province [LR16H090001]; Fundamental Research Funds for the Central Universities of ChinaFundamental Research Funds for the Central Universities Funding text: This work was supported by 111 project, grants from the National Natural Science Foundation of China (81371302 and 81571127 to WY), the National Basic Research Program of China (Grant Nos. 2013CB910204 to WY; 2014CB910300 to JL), Zhejiang Provincial Natural Science Foundation (LR16H090001 to WY), and Fundamental Research Funds for the Central Universities of China. Export Date: 7 January 2020 Correspondence Address: Yang, W.; Department of Neurobiology, Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn LA - English DB - MTMT ER - TY - JOUR AU - Poltronieri, Palmiro AU - Čerekovic, Nataša TI - Roles of nicotinamide adenine dinucleotide (NAD+) in biological systems JF - CHALLENGES J2 - CHALLENGES VL - 9 PY - 2018 IS - 1 SN - 2078-1547 DO - 10.3390/challe9010003 UR - https://m2.mtmt.hu/api/publication/30642560 ID - 30642560 LA - English DB - MTMT ER - TY - JOUR AU - Turlova, Ekaterina AU - Feng, Zhong-ping AU - Sun, Hong-shuo TI - The role of TRPM2 channels in neurons, glial cells and the blood-brain barrier in cerebral ischemia and hypoxia JF - ACTA PHARMACOLOGICA SINICA J2 - ACTA PHARMACOL SIN VL - 39 PY - 2018 IS - 5 SP - 713 EP - 721 PG - 9 SN - 1671-4083 DO - 10.1038/aps.2017.194 UR - https://m2.mtmt.hu/api/publication/27589549 ID - 27589549 N1 - Departments of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada Departments of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada Departments of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada Cited By :4 Export Date: 28 August 2019 CODEN: APSCG Correspondence Address: Feng, Z.-P.; Departments of Physiology, Faculty of Medicine, University of TorontoCanada; email: zp.feng@utoronto.ca Chemicals/CAS: TRPM Cation Channels; TRPM2 protein, human; TRPM2 protein, mouse Departments of Surgery, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada Departments of Physiology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada Departments of Pharmacology, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada Cited By :4 Export Date: 20 September 2019 CODEN: APSCG Correspondence Address: Feng, Z.-P.; Departments of Physiology, Faculty of Medicine, University of TorontoCanada; email: zp.feng@utoronto.ca Funding Agency and Grant Number: Natural Sciences and Engineering Research Council of Canada (NSERC)Natural Sciences and Engineering Research Council of Canada [RGPIN-2014-06471, RGPIN-2016-04574]; NSERC Alexander Graham Bell Canada Graduate Scholarship Funding text: This work was supported by the following grants: Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery Grants to Zhong-Ping FENG (RGPIN-2014-06471) and to Hong-Shuo SUN (RGPIN-2016-04574), and a NSERC Alexander Graham Bell Canada Graduate Scholarship to Ekaterina TURLOVA (CGS-D). Export Date: 7 January 2020 CODEN: APSCG Correspondence Address: Feng, Z.-P.; Departments of Physiology, Faculty of Medicine, University of TorontoCanada; email: zp.feng@utoronto.ca LA - English DB - MTMT ER - TY - JOUR AU - Vriens, Joris AU - Voets, Thomas TI - Sensing the heat with TRPM3 JF - PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY J2 - PFLUG ARCH EUR J PHY VL - 470 PY - 2018 IS - 5 SP - 799 EP - 807 PG - 9 SN - 0031-6768 DO - 10.1007/s00424-017-2100-1 UR - https://m2.mtmt.hu/api/publication/27609695 ID - 27609695 N1 - Cited By :32 Export Date: 18 April 2023 CODEN: PFLAB Correspondence Address: Vriens, J.; Laboratory of Endometrium, Herestraat 49, box 611, Belgium; email: Joris.Vriens@kuleuven.be LA - English DB - MTMT ER - TY - THES AU - Diercks, Björn-Philipp TI - Calcium microdomains during T lymphocyte activation–role of second messengers and calcium channels PY - 2017 UR - https://m2.mtmt.hu/api/publication/30642549 ID - 30642549 LA - English DB - MTMT ER - TY - JOUR AU - Fliegert, R AU - Bauche, A AU - Wolf, Pérez A-M AU - Watt, JM AU - Rozewitz, MD AU - Winzer, R AU - Janus, M AU - Gu, F AU - Rosche, A AU - Harneit, A AU - Flato, M AU - Moreau, C AU - Kirchberger, T AU - Wolters, V AU - Potter, BVL AU - Guse, AH TI - 2′-Deoxyadenosine 5′-diphosphoribose is an endogenous TRPM2 superagonist JF - NATURE CHEMICAL BIOLOGY J2 - NAT CHEM BIOL VL - 13 PY - 2017 IS - 9 SP - 1036 EP - 1044 PG - 9 SN - 1552-4450 UR - https://m2.mtmt.hu/api/publication/26954057 ID - 26954057 N1 - Funding Agency and Grant Number: Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [GU 360/16-1]; Wellcome TrustWellcome Trust [084068, 082837, 101010]; Landesforschungsforderung Hamburg (Research Group ReAd Me) Funding text: This study was supported by the Deutsche Forschungsgemeinschaft (GU 360/16-1 to A.H.G.), the Wellcome Trust (Project Grant 084068 to B.V.L.P. and A.H.G.; Programme Grant 082837 to B.V.L.P.) and Landesforschungsforderung Hamburg (Research Group ReAd Me to A.H.G.). B.V.L.P. is a Wellcome Trust Senior Investigator (grant 101010). Wild-type HEK293 cells were kindly provided by M. Jucker (Department of Biochemistry and Signal Transduction, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany). Expression plasmids pX330-Puro-T2A-hCas9 and pCAG-EGxxFP were kindly provided by A. Flugel (Department of Neuroimmunology, University Medical Center Gottingen, Gottingen, Germany). Export Date: 7 January 2020 CODEN: NCBAB Correspondence Address: Guse, A.H.; Calcium Signalling Group, Department of Biochemistry and Molecular Cell Biology, University Medical Centre Hamburg-EppendorfGermany; email: guse@uke.de LA - English DB - MTMT ER - TY - CHAP AU - Kashio, Makiko AU - Tominaga, Makoto ED - Mohammed, Awad Ali Khalid TI - Redox-Sensitive TRP Channels: TRPA1 and TRPM2 T2 - Redox PB - IntechOpen CY - London SN - 9789535133933 PY - 2017 SP - online DO - 10.5772/intechopen.69202 UR - https://m2.mtmt.hu/api/publication/30642562 ID - 30642562 LA - English DB - MTMT ER - TY - JOUR AU - Kashio, Makiko AU - Tominaga, Makoto TI - The TRPM2 channel: A thermo-sensitive metabolic sensor JF - CHANNELS J2 - CHANNELS VL - 11 PY - 2017 IS - 5 SP - 426 EP - 433 PG - 8 SN - 1933-6950 DO - 10.1080/19336950.2017.1344801 UR - https://m2.mtmt.hu/api/publication/27095257 ID - 27095257 N1 - Funding Agency and Grant Number: Ministry of Education, Culture, Sports, Science and Technology in JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [15H02501, 15H05928, 15K18974, 17K08543]; Salt Science and Mishima Kaiun Memorial Foundation [1634] Funding text: This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology in Japan (#15H02501 and #15H05928 to MT, and #15K18974 and #17K08543 to MK) and by Salt Science (#1634) and Mishima Kaiun Memorial Foundation to MK. Export Date: 7 January 2020 Correspondence Address: Tominaga, M.; Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Higashiyama 5–1, Myodaiji, Japan; email: tominaga@nips.ac.jp Export Date: 8 January 2020 Correspondence Address: Tominaga, M.; Division of Cell Signaling, Okazaki Institute for Integrative Bioscience (National Institute for Physiological Sciences), Higashiyama 5–1, Myodaiji, Japan; email: tominaga@nips.ac.jp LA - English DB - MTMT ER - TY - JOUR AU - Kuehn, Frank AU - Kuehn, Cornelia AU - Lueckhoff, Andreas TI - Different Principles of ADP-Ribose-Mediated Activation and Opposite Roles of the NUDT9 Homology Domain in the TRPM2 Orthologs of Man and Sea Anemone JF - FRONTIERS IN PHYSIOLOGY J2 - FRONT PHYSIOL VL - 8 PY - 2017 PG - 14 SN - 1664-042X DO - 10.3389/fphys.2017.00879 UR - https://m2.mtmt.hu/api/publication/27095255 ID - 27095255 LA - English DB - MTMT ER - TY - JOUR AU - Li, Jun AU - Gao, Yunling AU - Bao, Xianying AU - Li, Fengna AU - Yao, Wei AU - Feng, Zemeng AU - Yin, Yulong TI - TRPM2: a potential drug target to retard oxidative stress JF - FRONTIERS IN BIOSCIENCE-LANDMARK J2 - FRONT BIOSCI-LANDMARK VL - 22 PY - 2017 SP - 1427 EP - 1438 PG - 12 SN - 2768-6701 DO - 10.2741/4551 UR - https://m2.mtmt.hu/api/publication/26578581 ID - 26578581 N1 - Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, National Engineering Laboratory for Pollution Control, Waste Utilization in Livestock and Poultry Production, Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production, Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture, Changsha, Hunan, 410125, China Xiangyang Central Hospital, Affliated Hospital of Hubei University of Arts and Science, Xiangyang441021, China College of Animal Science and Technology, Hunan Agricultural University, Changsha, 410128, China University of Chinese Academy of Sciences, Beijing, 100049, China Department of Cardiology, Tianjin Medical University General Hospital, Tianjin Medial University, Tianjin, 300052, China Hunan Co-Innovation Center of Animal Production Safety, CICAPS, Changsha, 410128, China Cited By :8 Export Date: 20 September 2019 Correspondence Address: Feng, Z.Mapoling of Changsha City, China; email: zemengfeng2006@163.com Funding Agency and Grant Number: Chinese Academy of Science STS Project [KFJ-SW-STS-173]; National "948" Project from the Ministry of Agriculture of China [2015Z74]; international Partnership Program of Chinese Academy of Sciences grant [161343KYSB20160008]; Science and Technology Development Fund Project of Tianjin [20130138] Funding text: Jun Li and Yunling Gao contributed equally to this work. Thank Dr. Yun Su for her figures drawing work. This research was jointly supported by the Chinese Academy of Science STS Project (KFJ-SW-STS-173), the National "948" Project from the Ministry of Agriculture of China (2015Z74), the international Partnership Program of Chinese Academy of Sciences grant (161343KYSB20160008), and Science and Technology Development Fund Project of Tianjin (20130138). Export Date: 7 January 2020 Correspondence Address: Feng, Z.Mapoling of Changsha City, China; email: zemengfeng2006@163.com LA - English DB - MTMT ER - TY - JOUR AU - Long, Aaron AU - Klimova, Nina AU - Kristian, Tibor TI - Mitochondrial NUDIX hydrolases: A metabolic link between NAD catabolism, GTP and mitochondrial dynamics JF - NEUROCHEMISTRY INTERNATIONAL J2 - NEUROCHEM INT VL - 109 PY - 2017 SP - 193 EP - 201 PG - 9 SN - 0197-0186 DO - 10.1016/j.neuint.2017.03.009 UR - https://m2.mtmt.hu/api/publication/27095502 ID - 27095502 N1 - Cited By :5 Export Date: 20 December 2018 CODEN: NEUID Correspondence Address: Kristian, T.; Department of Anesthesiology School of Medicine, University of Maryland Baltimore, 685 W. Baltimore Street, MSTF 534, United States; email: tkristian@anes.umm.edu Cited By :9 Export Date: 28 August 2019 CODEN: NEUID Correspondence Address: Kristian, T.; Department of Anesthesiology School of Medicine, University of Maryland Baltimore, 685 W. Baltimore Street, MSTF 534, United States; email: tkristian@anes.umm.edu Chemicals/CAS: adenine nucleotide translocase, 9068-80-8; adenosine diphosphate ribose, 20762-30-5; adenosine phosphate, 61-19-8, 8063-98-7; adenylate kinase, 9013-02-9; glycosidase, 9032-92-2; guanosine triphosphate, 86-01-1; hydroxymethylglutaryl coenzyme A reductase kinase, 172522-01-9, 72060-32-3; nicotinamide adenine dinucleotide, 53-84-9; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase, 58319-92-9; poly(adenosine diphosphate ribose), 26656-46-2; protein, 67254-75-5; reduced nicotinamide adenine dinucleotide, 58-68-4; inorganic pyrophosphatase, 9024-82-2, 9033-44-7; Guanosine Triphosphate; NAD; nudix hydrolases; Pyrophosphatases Cited By :9 Export Date: 20 September 2019 CODEN: NEUID Correspondence Address: Kristian, T.; Department of Anesthesiology School of Medicine, University of Maryland Baltimore, 685 W. Baltimore Street, MSTF 534, United States; email: tkristian@anes.umm.edu Funding Agency and Grant Number: U.S. Veterans Affairs [BX000917] Funding text: This work was supported by U.S. Veterans Affairs Merit grant BX000917 to TK. Export Date: 7 January 2020 CODEN: NEUID Correspondence Address: Kristian, T.; Department of Anesthesiology School of Medicine, University of Maryland Baltimore, 685 W. Baltimore Street, MSTF 534, United States; email: tkristian@anes.umm.edu LA - English DB - MTMT ER - TY - JOUR AU - Morales-Lázaro, Sara L AU - Lemus, Luis AU - Rosenbaum, Tamara TI - Regulation of thermoTRPs by lipids. JF - TEMPERATURE J2 - TEMPERATURE VL - 4 PY - 2017 IS - 1 SP - 24 EP - 40 PG - 17 SN - 2332-8940 DO - 10.1080/23328940.2016.1254136 UR - https://m2.mtmt.hu/api/publication/30391215 ID - 30391215 N1 - Journal Article; Review Cited By :2 Export Date: 20 September 2019 Correspondence Address: Morales-Lázaro, S.L.; Department of Cognitive Neuroscience, Instituto de Fisiología Celular, Circuito exterior s/n, Universidad Nacional Autónoma de México, CoyoacanMexico; email: saraluzm@ifc.unam.mx Export Date: 7 January 2020 Correspondence Address: Morales-Lázaro, S.L.; Department of Cognitive Neuroscience, Instituto de Fisiología Celular, Circuito exterior s/n, Universidad Nacional Autónoma de México, CoyoacanMexico; email: saraluzm@ifc.unam.mx AB - The family of Transient Receptor Potential (TRP) ion channels is constituted by 7 subfamilies among which are those that respond to temperature, the thermoTRPs. These channels are versatile molecules of a polymodal nature that have been shown to be modulated in various fashions by molecules of a lipidic nature. Some of these molecules interact directly with the channels on specific regions of their structures and some of these promote changes in membrane fluidity or modify their gating properties in response to their agonists. Here, we have discussed how some of these lipids regulate the activity of thermoTRPs and included some of the available evidence for the molecular mechanisms underlying their effects on these channels. LA - English DB - MTMT ER - TY - CHAP AU - Philippaert, K. AU - Vennekens, R. ED - Rosenbaum Emir, Tamara Luti TI - The role of TRP channels in the pancreatic beta-cell T2 - Neurobiology of TRP Channels PB - CRC Press CY - Boca Raton, Florida SN - 9781315152837 PY - 2017 SP - 229 EP - 250 PG - 22 DO - 10.4324/9781315152837-12 UR - https://m2.mtmt.hu/api/publication/30797792 ID - 30797792 AB - Diabetes is the most common metabolic disease in humans. The hallmark of diabetes is an elevated blood glucose concentration, but this abnormality is just one of many biochemical and physiological alterations that occur in the disease. Both genetic and environmental factors contribute to its pathogenesis, which involves insufcient insulin secretion, reduced responsiveness to endogenous or exogenous insulin, increased glucose production, and/or abnormalities in fat and protein metabolism. Diabetes is not one distinct disorder, but it can arise as a result of numerous defects in regulation of the synthesis, secretion, and action of insulin. In type I diabetes, idiopathic or immune-mediated β -cell destruction lies at the basis of complete insulin deciency (Thompson Coon, 2010). In type II diabetes, the cause of hyperglycemia is more complex. It ranges from predominantly insulin resistance with relative insulin deciency to a predominantly insulin secretory defect with insulin resistance. There are several genetic defects that are risk factors toward the development of type II diabetes such as functional alterations of transient receptor potential (TRP) channels. Furthermore, there is a connection between old age, a high-calorie diet, and diabetes type II (Herder and Roden, 2011). Mice studies revealed that feeding a high-fat diet leads to gradual development of obesity (Hariri and Thibault, 2010), glucose intolerance through insulin resistance, and ultimately diabetes (Winzell and Ahrén, 2004). A subset of type II diabetic patients develops hyperglycemia secondary to hypoinsulinemia instead of peripheral insulin resistance (Ashcroft and Rorsman, 2013; Pende et al., 2000; Phillips, 1996). This can be induced by either β -cell dysfunction or loss of functional β -cell mass (Peiris et al., 2012). Patients with type II diabetes are usually treated with pharmacologic agents in combination with lifestyle modications (Lebovitz, 2011). The used pharmaceuticals. © 2018 by Taylor & Francis Group, LLC. LA - English DB - MTMT ER - TY - CHAP AU - Sawamura, S. AU - Shirakawa, H. AU - Nakagawa, T. AU - Mori, Y. AU - Kaneko, S. ED - Rosenbaum Emir, Tamara Luti TI - TRP channels in the brain: What are they there for? T2 - Neurobiology of TRP Channels PB - CRC Press CY - Boca Raton, Florida SN - 9781315152837 PY - 2017 SP - 295 EP - 322 PG - 28 DO - 10.4324/9781315152837 UR - https://m2.mtmt.hu/api/publication/31916627 ID - 31916627 AB - Transient receptor potential (TRP) family proteins form tetrameric nonselective cation channels. Upon activation, TRP channels depolarize the membrane potential, which can lead to activation or inactivation of voltage-gated ion channels, and regulate Ca2+ signaling, which controls diverse cellular functions (Wu et al., 2010; Nilius and Szallasi, 2014). It is well known that some members of the TRP canonical (TRPC), TRP melastatin (TRPM), and TRP vanilloid (TRPV) subfamilies of TRP channels are highly expressed and play important roles in the brain (Vennekens et al., 2012; Nilius and Szallasi, 2014). They regulate diverse neuronal and glial functions including developmental and homeostatic functions of the brain. Recent studies show that dysregulation of the TRP channel functions is involved in various pathological events of neurological and psychiatric disorders. Here, we review the current insights of the physiological roles of the TRPC, TRPM, and TRPV channels, mainly TRPC3/TRPC6/TRPC7, TRPM2, and TRPV1 in neurons and glia, and their pathophysiological roles in neurological and psychiatric disorders. © 2018 by Taylor & Francis Group, LLC. LA - English DB - MTMT ER - TY - JOUR AU - Yu, P AU - Xue, X AU - Zhang, J AU - Hu, X AU - Wu, Y AU - Jiang, L-H AU - Jin, H AU - Luo, J AU - Zhang, L AU - Liu, Z AU - Yang, W TI - Identification of the ADPR binding pocket in the NUDT9 homology domain of TRPM2 JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 149 PY - 2017 IS - 2 SP - 219 EP - 235 PG - 17 SN - 0022-1295 DO - 10.1085/jgp.201611675 UR - https://m2.mtmt.hu/api/publication/26497564 ID - 26497564 N1 - Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310058, China Department of Toxicology, School of Public Health, Zhejiang University, Hangzhou, Zhejiang, 310058, China State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, China School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds, Leeds, England, LS2 9JT, United Kingdom Department of Physiology and Neurobiology, Xinxiang Medical University, Henan, 453003, China Sino-UK Brain Function Laboratory, Xinxiang Medical University, Henan, 453003, China Cited By :16 Export Date: 20 September 2019 CODEN: JGPLA Correspondence Address: Yang, W.; Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn Funding Agency and Grant Number: National Basic Research Program of ChinaNational Basic Research Program of China [2013CB910204, 2014CB910300]; Natural Science Foundation of ChinaNational Natural Science Foundation of China [21402171] Funding text: This work was supported by grants from the National Basic Research Program of China (2013CB910204 to W. Yang and 2014CB910300 to J. Luo) and the Natural Science Foundation of China (21402171 to P. Yu). Export Date: 7 January 2020 CODEN: JGPLA Correspondence Address: Yang, W.; Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn Export Date: 8 January 2020 CODEN: JGPLA Correspondence Address: Yang, W.; Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang University School of MedicineChina; email: yangwei@zju.edu.cn LA - English DB - MTMT ER - TY - JOUR AU - Bao, L AU - Chen, S-J AU - Conrad, K AU - Keefer, K AU - Abraham, T AU - Lee, JP AU - Wang, J AU - Zhang, X-Q AU - Hirschler-Laszkiewicz, I AU - Wang, H-G AU - Dovat, S AU - Gans, B AU - Madesh, M AU - Cheung, JY AU - Miller, BA TI - Depletion of the human ion channel TRPM2 in neuroblastoma demonstrates its key role in cell survival through modulation of mitochondrial reactive oxygen species and bioenergetics JF - JOURNAL OF BIOLOGICAL CHEMISTRY J2 - J BIOL CHEM VL - 291 PY - 2016 IS - 47 SP - 24449 EP - 24464 PG - 16 SN - 0021-9258 DO - 10.1074/jbc.M116.747147 UR - https://m2.mtmt.hu/api/publication/26362985 ID - 26362985 N1 - Funding Agency and Grant Number: National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [RO1-GM117014, RO1-DK46778, RO1-HL-58672, RO1-HL74854, RO1-HL123093, R01GM109882, R01HL086699, R01HL119306, 1S10RR027327]; Hyundai Hope on Wheels; Four Diamonds Fund of the Pennsylvania State University; American Heart AssociationAmerican Heart Association [15GRNT25680042]; PA CURE Grant [4100062220] Funding text: This work was supported in part by National Institutes of Health Grants RO1-GM117014 and RO1-DK46778 (to B. A. M.), RO1-HL-58672, RO1-HL74854, and RO1-HL123093 (to J. Y. C.), R01GM109882, R01HL086699, R01HL119306, and 1S10RR027327 (to M. M.), grants from the Hyundai Hope on Wheels, the Four Diamonds Fund of the Pennsylvania State University, American Heart Association (Great Rivers Affiliate) Grant-in-aid 15GRNT25680042, and PA CURE Grant (Project 5) SAP#4100062220. The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Export Date: 7 January 2020 CODEN: JBCHA Correspondence Address: Miller, B.A.; Dept. of Pediatrics, Milton S. Hershey Medical Center, P.O. Box 850, United States; email: bmiller3@psu.edu LA - English DB - MTMT ER - TY - THES AU - Coyle, Jayme TI - The influence of oxygen tension and glycolytic and citric acid cycle substrates in acrolein-induced cellular injury in the differentiated H9c2 cardiac cell model PY - 2016 UR - https://m2.mtmt.hu/api/publication/30642541 ID - 30642541 LA - English DB - MTMT ER - TY - JOUR AU - Feng, Xinghua AU - Yang, Junsheng TI - Lysosomal Calcium in Neurodegeneration. JF - Messenger (Los Angeles, Calif. : Print) J2 - Messenger (Los Angel) VL - 5 PY - 2016 IS - 1-2 SP - 56 EP - 66 PG - 11 SN - 2167-955X DO - 10.1166/msr.2016.1055 UR - https://m2.mtmt.hu/api/publication/30391214 ID - 30391214 AB - Lysosomes are the central organelles responsible for macromolecule recycling in the cell. Lysosomal dysfunction is the primary cause of lysosomal storage diseases (LSDs), and contributes significantly to the pathogenesis of common neurodegenerative diseases. The lysosomes are also intracellular stores for calcium ions, one of the most common second messenger in the cell. Lysosomal Ca2+ is required for diverse cellular processes including signal transduction, vesicular trafficking, autophagy, nutrient sensing, exocytosis, and membrane repair. In this review, we first summarize some recent progresses in the studies of lysosome Ca2+ regulation, with a focus on the newly discovered lysosomal Ca2+ channels and the mechanisms of lysosomal Ca2+ store refilling. We then discuss how defects in lysosomal Ca2+ release and store maintenance cause lysosomal dysfunction and neurodegeneration. LA - English DB - MTMT ER - TY - JOUR AU - Guse, AH AU - Wolf, IMA TI - Ca2+ microdomains, NAADP and type 1 ryanodine receptor in cell activation JF - BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH J2 - BBA-MOL CELL RES VL - 1863 PY - 2016 IS - 6 SP - 1379 EP - 1384 PG - 6 SN - 0167-4889 DO - 10.1016/j.bbamcr.2016.01.014 UR - https://m2.mtmt.hu/api/publication/25812315 ID - 25812315 LA - English DB - MTMT ER - TY - JOUR AU - Iordanov, Iordan AU - Mihályi, Csaba AU - Tóth, Balázs AU - Csanády, László TI - The proposed channel-enzyme transient receptor potential melastatin 2 does not possess ADP ribose hydrolase activity JF - ELIFE J2 - ELIFE VL - 5 PY - 2016 PG - 20 SN - 2050-084X DO - 10.7554/eLife.17600 UR - https://m2.mtmt.hu/api/publication/3105008 ID - 3105008 N1 - Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary MTA-SE Ion Channel Research Group, Semmelweis University, Budapest, Hungary Cited By :17 Export Date: 20 September 2019 Correspondence Address: Csanády, L.; Department of Medical Biochemistry, Semmelweis UniversityHungary; email: csanady.laszlo@med.semmelweis-univ.hu Funding Agency and Grant Number: Howard Hughes Medical Institute International Early Career Scientist [55007416]; Magyar Tudomanyos Akademia Lendulet [LP2012-39/2012] Funding text: Howard Hughes Medical Institute International Early Career Scientist grant, 55007416 Laszlo Csanady; Magyar Tudomanyos Akademia Lendulet grant, LP2012-39/2012 Laszlo Csanady Export Date: 7 January 2020 Correspondence Address: Csanády, L.; Department of Medical Biochemistry, Semmelweis UniversityHungary; email: csanady.laszlo@med.semmelweis-univ.hu LA - English DB - MTMT ER - TY - JOUR AU - Kuehn, Frank J P AU - Kuehn, Cornelia AU - Winking, Mathis AU - Hoffmann, Daniel C AU - Lueckhoff, Andreas TI - ADP-Ribose Activates the TRPM2 Channel from the Sea Anemone Nematostella vectensis Independently of the NUDT9H Domain JF - PLOS ONE J2 - PLOS ONE VL - 11 PY - 2016 IS - 6 PG - 21 SN - 1932-6203 DO - 10.1371/journal.pone.0158060 UR - https://m2.mtmt.hu/api/publication/26029746 ID - 26029746 N1 - Cited By :8 Export Date: 20 September 2019 CODEN: POLNC Funding Agency and Grant Number: Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [KU 2271/4-1] Funding text: The study was supported by the Deutsche Forschungsgemeinschaft (www.dfg.de), grant number: KU 2271/4-1 to FK. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Export Date: 7 January 2020 CODEN: POLNC LA - English DB - MTMT ER - TY - JOUR AU - Li, F-Y AU - Wong, R AU - Turlova, E AU - Sun, H-S TI - Pathological role of transient receptor potential melastatin member 2 channel in neurodegenerative diseases and Alzheimer disease JF - CHINESE JOURNAL OF PHARMACOLOGY AND TOXICOLOGY / ZHONG GUO YAO LI XUE YU DU LI XUE ZA ZHI J2 - CHINESE J PHARM TOXICOL VL - 30 PY - 2016 IS - 6 SP - 656 EP - 666 PG - 11 SN - 1000-3002 DO - 10.3867/j.issn.1000-3002.2016.06.005 UR - https://m2.mtmt.hu/api/publication/26178279 ID - 26178279 N1 - Export Date: 7 January 2020 CODEN: ZYYZE Correspondence Address: Sun, H.-S.; Department of Physiology, University of TorontoCanada; email: hss.sun@utoronto.ca LA - English DB - MTMT ER - TY - JOUR AU - Ogawa, Nozomi AU - Kurokawa, Tatsuki AU - Mori, Yasuo TI - Sensing of redox status by TRP channels JF - CELL CALCIUM J2 - CELL CALCIUM VL - 60 PY - 2016 IS - 2 SP - 115 EP - 122 PG - 8 SN - 0143-4160 DO - 10.1016/j.ceca.2016.02.009 UR - https://m2.mtmt.hu/api/publication/26170511 ID - 26170511 N1 - Funding Agency and Grant Number: Ministry of Education, Culture, Sports, Science and Technology, JapanMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT) [26111004]; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [24249017] Funding text: This work was supported by a Grant-in-Aid for Scientific Research on Innovative Areas "Oxygen biology: a new criterion for integrated understanding of life" [26111004] of The Ministry of Education, Culture, Sports, Science and Technology, Japan; and a Grant-in-Aid for Scientific Research (A) [24249017] of Japan Society for the Promotion of Science. Export Date: 7 January 2020 CODEN: CECAD Correspondence Address: Mori, Y.; Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniversityJapan; email: mori@sbchem.kyoto-u.ac.jp Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, 615-8510, Japan Laboratory of Environmental Systems Biology, Department of Technology and Ecology, Hall of Global Environmental Studies, Kyoto University, Kyoto, 615-8510, Japan Cited By :30 Export Date: 29 January 2020 CODEN: CECAD Correspondence Address: Mori, Y.; Laboratory of Molecular Biology, Department of Synthetic Chemistry and Biological Chemistry, Graduate School of Engineering, Kyoto UniversityJapan; email: mori@sbchem.kyoto-u.ac.jp LA - English DB - MTMT ER - TY - JOUR AU - Rack, Johannes Gregor Matthias AU - Perina, Dragutin AU - Ahel, Ivan TI - Macrodomains: Structure, Function, Evolution, and Catalytic Activities JF - ANNUAL REVIEW OF BIOCHEMISTRY J2 - ANNU REV BIOCHEM VL - 85 PY - 2016 SP - 431 EP - 454 PG - 24 SN - 0066-4154 DO - 10.1146/annurev-biochem-060815-014935 UR - https://m2.mtmt.hu/api/publication/32161073 ID - 32161073 AB - Recent developments indicate that macrodomains, an ancient and diverse protein domain family, are key players in the recognition, interpretation, and turnover of ADP-ribose (ADPr) signaling. Crucial to this is the ability of macrodomains to recognize ADPr either directly, in the form of a metabolic derivative, or as a modification covalently bound to proteins. Thus, macrodomains regulate a wide variety of cellular and organismal processes, including DNA damage repair, signal transduction, and immune response. Their importance is further indicated by the fact that dysregulation or mutation of a macrodomain is associated with several diseases, including cancer, developmental defects, and neurodegeneration. In this review, we summarize the current insights into macrodomain evolution and how this evolution influenced their structural and functional diversification. We highlight some aspects of macrodomain roles in pathobiology as well as their emerging potential as therapeutic targets. © Copyright 2016 by Annual Reviews. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Wang, Gang AU - Cao, Luyang AU - Liu, Xiaowen AU - Sieracki, Nathan A AU - Di, Anke AU - Wen, Xi AU - Chen, Yong AU - Taylor, Shalina AU - Huang, Xiaojia AU - Tiruppathi, Chinnaswamy AU - Zhao, You-yang AU - Song, Yuanlin AU - Gao, Xiaopei AU - Jin, Tian AU - Bai, Chunxue AU - Malik, Asrar B AU - Xu, Jingsong TI - Oxidant Sensing by TRPM2 Inhibits Neutrophil Migration and Mitigates Inflammation JF - DEVELOPMENTAL CELL J2 - DEV CELL VL - 38 PY - 2016 IS - 5 SP - 453 EP - 462 PG - 10 SN - 1534-5807 DO - 10.1016/j.devcel.2016.07.014 UR - https://m2.mtmt.hu/api/publication/26170512 ID - 26170512 N1 - Funding Agency and Grant Number: NHLBI NIH HHSUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Heart Lung & Blood Institute (NHLBI) [R01 HL122157] Export Date: 7 January 2020 CODEN: DCEEB Correspondence Address: Xu, J.; Department of Pharmacology, University of IllinoisUnited States; email: jingsong.xu@hotmail.com LA - English DB - MTMT ER - TY - JOUR AU - Yamamoto, S AU - Shimizu, S TI - Targeting TRPM2 in ROS-Coupled diseases JF - PHARMACEUTICALS J2 - PHARMACEUTICALS-BASE VL - 9 PY - 2016 IS - 3 SN - 1424-8247 DO - 10.3390/ph9030057 UR - https://m2.mtmt.hu/api/publication/26248229 ID - 26248229 N1 - Export Date: 7 January 2020 Correspondence Address: Shimizu, S.; Division of Pharmacology, Faculty of Pharmaceutical Sciences, Teikyo Heisei UniversityJapan; email: s.shimizu@thu.ac.jp LA - English DB - MTMT ER - TY - JOUR AU - Rosenbaum, Tamara TI - Activators of TRPM2: Getting it right JF - JOURNAL OF GENERAL PHYSIOLOGY J2 - J GEN PHYSIOL VL - 145 PY - 2015 IS - 6 SP - 485 EP - 487 PG - 3 SN - 0022-1295 DO - 10.1085/jgp.201511405 UR - https://m2.mtmt.hu/api/publication/25361599 ID - 25361599 N1 - Export Date: 7 January 2020 CODEN: JGPLA Correspondence Address: Rosenbaum, T.; Departamento de Neurodesarrollo y Fisiología, División Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de MéxicoMexico; email: trosenba@ifc.unam.mx LA - English DB - MTMT ER -