TY - JOUR AU - Bartók, Ádám AU - Csanády, László TI - TRPM2 - an adjustable thermostat JF - CELL CALCIUM J2 - CELL CALCIUM VL - 118 PY - 2024 PG - 6 SN - 0143-4160 DO - 10.1016/j.ceca.2024.102850 UR - https://m2.mtmt.hu/api/publication/34502176 ID - 34502176 LA - English DB - MTMT ER - TY - JOUR AU - Tóth, Ádám Viktor AU - Bartók, Ádám TI - Reviewing critical TRPM2 variants through a structure-function lens JF - JOURNAL OF BIOTECHNOLOGY J2 - J BIOTECHNOL PY - 2024 SN - 0168-1656 DO - 10.1016/j.jbiotec.2024.02.017 UR - https://m2.mtmt.hu/api/publication/34720489 ID - 34720489 LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám TI - Investigation of factors that influence the temperature sensitivity of the TRPM2 cation channel JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 122 PY - 2023 IS - 3S1 SP - 110a EP - 110a SN - 0006-3495 DO - 10.1016/j.bpj.2022.11.775 UR - https://m2.mtmt.hu/api/publication/33666263 ID - 33666263 N1 - Export Date: 27 February 2023 LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám AU - Csanady, Laszlo TI - The molecular nature of temperature dependence of the TRPM2 channel JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 121 PY - 2022 IS - 3 SP - 14 EP - 14 PG - 1 SN - 0006-3495 DO - 10.1016/j.bpj.2021.11.2634 UR - https://m2.mtmt.hu/api/publication/32720668 ID - 32720668 LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám AU - Csanády, László TI - Dual amplification strategy turns TRPM2 channels into supersensitive central heat detectors JF - PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA J2 - P NATL ACAD SCI USA VL - 119 PY - 2022 IS - 48 PG - 11 SN - 0027-8424 DO - 10.1073/pnas.2212378119 UR - https://m2.mtmt.hu/api/publication/33262968 ID - 33262968 N1 - Hungarian Centre of Excellence for Molecular Medicine-Semmelweis Egyetem (HCEMM-SE), Molecular Channelopathies Research Group, Semmelweis University, Budapest, H-1094, Hungary Magyar Tudományos Akadémia-Semmelweis Egyetem (MTA-SE), Ion Channel Research Group, Semmelweis University, Budapest, H-1094, Hungary Department of Biochemistry, Semmelweis University, Budapest, H-1094, Hungary Cited By :3 Export Date: 4 September 2023 CODEN: PNASA Correspondence Address: Csanády, L.; Hungarian Centre of Excellence for Molecular Medicine-Semmelweis Egyetem (HCEMM-SE), Hungary; email: csanady.laszlo@med.semmelweis-univ.hu Chemicals/CAS: adenosine diphosphate ribose, 20762-30-5; calcium ion, 14127-61-8; hydrogen peroxide, 7722-84-1; calcium, 7440-70-2, 14092-94-5; Adenosine Diphosphate Ribose; Calcium; Hydrogen Peroxide; TRPM Cation Channels Funding details: 739593 Funding details: GINOP-2.3.2-15-2016-00051 Funding details: ÚNKP-20-5-SE-6, ÚNKP-21-5-SE-10 Funding details: Magyar Tudományos Akadémia, MTA, BO/00103/20, LP2017-14/2017 Funding details: Nemzeti Kutatási Fejlesztési és Innovációs Hivatal, NKFIH Funding text 1: We thank Beáta Töröcsik for subcloning T5L-TRPM2 into pcDNA3, Iordan Iordanov for providing purified nvNUDT9H, and Katalin Zboray (Agricultural Institute, Centre for Agricultural Research, Martonvásár, Hungary) for providing the stable T5L TRPM2 cell line (Economic Development and Innovation Operational Programme (GINOP-2.3.2-15-2016-00051) of the National Research, Development and Innovation Office). Support was provided by EU Horizon 2020 Research and Innovation Program grant 739593 and MTA Lendület grant LP2017-14/2017 to L.C. and a New National Excellence Program (ÚNKP) award of the Ministry of Human Capacities of Hungary to Semmelweis University. Á.B. was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00103/20) and the New National Excellence Program (ÚNKP) Bolyai+ scholarship of the Ministry of Human Capacities of Hungary (ÚNKP-20-5-SE-6 and ÚNKP-21-5-SE-10). Funding text 2: ACKNOWLEDGMENTS. We thank Beáta Töröcsik for subcloning T5L-TRPM2 into pcDNA3, Iordan Iordanov for providing purified nvNUDT9H, and Katalin Zboray (Agricultural Institute, Centre for Agricultural Research, Martonvásár, Hungary) for providing the stableT5LTRPM2 cell line (Economic Development and Innovation Operational Programme (GINOP-2.3.2-15-2016-00051) of the National Research, Development and Innovation Office). Support was provided by EU Horizon 2020 Research and Innovation Program grant 739593 and MTA Lendület grant LP2017-14/2017 to L.C. and a New National Excellence Program (ÚNKP) award of the Ministry of Human Capacities of Hungary to Semmelweis University. Á.B. was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00103/20) and the New National Excellence Program (ÚNKP) Bolyai+ scholarship of the Ministry of Human Capacities of Hungary (ÚNKP-20-5-SE-6 and ÚNKP-21-5-SE-10). AB - The Ca 2+ and ADP ribose (ADPR)-activated cation channel TRPM2 is the closest homolog of the cold sensor TRPM8 but serves as a deep-brain warmth sensor. To unravel the molecular mechanism of heat sensing by the TRPM2 protein, we study here temperature dependence of TRPM2 currents in cell-free membrane patches across ranges of agonist concentrations. We find that channel gating remains strictly agonist-dependent even at 40°C: heating alone or in combination with just Ca 2+ , just ADPR, Ca 2+ + cyclic ADPR, or H 2 O 2 pretreatment only marginally activates TRPM2. For fully liganded TRPM2, pore opening is intrinsically endothermic, due to ~10-fold larger activation enthalpy for opening (~200 kJ/mol) than for closure (~20 kJ/mol). However, the temperature threshold is too high (>40°C) for unliganded but too low (<15°C) for fully liganded channels. Thus, warmth sensitivity around 37°C is restricted to narrow ranges of agonist concentrations. For ADPR, that range matches, but for Ca 2+ , it exceeds bulk cytosolic values. The supraphysiological [Ca 2+ ] needed for TRPM2 warmth sensitivity is provided by Ca 2+ entering through the channel’s pore. That positive feedback provides further strong amplification to the TRPM2 temperature response (Q 10 ~ 1,000), enabling the TRPM2 protein to autonomously respond to tiny temperature fluctuations around 37°C. These functional data together with published structures suggest a molecular mechanism for opposite temperature dependences of two closely related channel proteins. LA - English DB - MTMT ER - TY - JOUR AU - Katona, Máté AU - Bartók, Ádám AU - Nichtova, Zuzana AU - Csordás, György AU - Berezhnaya, Elena AU - Weaver, David AU - Ghosh, Arijita AU - Várnai, Péter AU - Yule, David I. AU - Hajnóczky, György TI - Capture at the ER-mitochondrial contacts licenses IP3 receptors to stimulate local Ca2+ transfer and oxidative metabolism JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 13 PY - 2022 IS - 1 PG - 11 SN - 2041-1723 DO - 10.1038/s41467-022-34365-8 UR - https://m2.mtmt.hu/api/publication/33225777 ID - 33225777 N1 - Export Date: 20 April 2023 Correspondence Address: Hajnóczky, G.; MitoCare Center, United States; email: gyorgy.hajnoczky@jefferson.edu AB - Endoplasmic reticulum-mitochondria contacts (ERMCs) are restructured in response to changes in cell state. While this restructuring has been implicated as a cause or consequence of pathology in numerous systems, the underlying molecular dynamics are poorly understood. Here, we show means to visualize the capture of motile IP 3 receptors (IP3Rs) at ERMCs and document the immediate consequences for calcium signaling and metabolism. IP3Rs are of particular interest because their presence provides a scaffold for ERMCs that mediate local calcium signaling, and their function outside of ERMCs depends on their motility. Unexpectedly, in a cell model with little ERMC Ca 2+ coupling, IP3Rs captured at mitochondria promptly mediate Ca 2+ transfer, stimulating mitochondrial oxidative metabolism. The Ca 2+ transfer does not require linkage with a pore-forming protein in the outer mitochondrial membrane. Thus, motile IP3Rs can traffic in and out of ERMCs, and, when ‘parked’, mediate calcium signal propagation to the mitochondria, creating a dynamic arrangement that supports local communication. LA - English DB - MTMT ER - TY - JOUR AU - Raghavendra, Singh AU - Bartók, Ádám AU - Melanie, Paillard AU - Ashley, Tyburski AU - Melanie, Elliott AU - György, Hajnóczky TI - Uncontrolled mitochondrial calcium uptake underlies the pathogenesis of neurodegeneration in MICU1-deficient mice and patients JF - SCIENCE ADVANCES J2 - SCI ADV VL - 8 PY - 2022 IS - 11 PG - 13 SN - 2375-2548 DO - 10.1126/sciadv.abj4716 UR - https://m2.mtmt.hu/api/publication/32711156 ID - 32711156 LA - English DB - MTMT ER - TY - JOUR AU - Kohlschmidt, Nicolai AU - Elbracht, Miriam AU - Czech, Artur AU - Häusler, Martin AU - Phan, Vietxuan AU - Töpf, Ana AU - Huang, Kai‐Ting AU - Bartók, Ádám AU - Eggermann, Katja AU - Zippel, Stephanie AU - Eggermann, Thomas AU - Freier, Erik AU - Groß, Claudia AU - Lochmüller, Hanns AU - Horvath, Rita AU - Hajnóczky, György AU - Weis, Joachim AU - Roos, Andreas TI - Molecular pathophysiology of human MICU1‐deficiency JF - NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY J2 - NEUROPATH APPL NEURO VL - 47 PY - 2021 IS - 6 SP - 840 EP - 855 PG - 16 SN - 0305-1846 DO - 10.1111/nan.12694 UR - https://m2.mtmt.hu/api/publication/31819232 ID - 31819232 LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám AU - Weaver, David AU - Golenár, Tünde AU - Nichtova, Zuzana AU - Katona, Máté AU - Bánsághi, Száva AU - Alzayady, Kamil J. AU - Thomas, V. Kaye AU - Ando, Hideaki AU - Mikoshiba, Katsuhiko AU - Joseph, Suresh K. AU - Yule, David I. AU - Csordás, György AU - Hajnóczky, György TI - IP3 receptor isoforms differently regulate ER-mitochondrial contacts and local calcium transfer JF - NATURE COMMUNICATIONS J2 - NAT COMMUN VL - 10 PY - 2019 IS - 1 PG - 14 SN - 2041-1723 DO - 10.1038/s41467-019-11646-3 UR - https://m2.mtmt.hu/api/publication/30767645 ID - 30767645 N1 - Funding Agency and Grant Number: NIH [S10ODO23440, DK051526, GM059419, ES025672, DK103558, DE014756]; Hungarian State Eotvos Fellowship from the Tempus Public Foundation (Hungary) Funding text: We thank Dr. T. Kurosaki for providing us with DT40 cells. Adam Bartok was supported by a Hungarian State Eotvos Fellowship from the Tempus Public Foundation (Hungary). This study was funded by NIH grants DK051526 and GM059419 (G.H.), ES025672 (G.H. and G.C.), DK103558 (S.K.J. and G.H.), and DE014756 (DIY). The Abberior STED microscope was partially funded by NIH S10ODO23440 (D.I.Y.). MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA, United States Departent of Medical Biochemistry, Semmelweis University, Budapest, Hungary Department of Physiology and Pharmacology, University of Rochester, Rochester, NY, United States Lab for Developmental Neurobiology, RIKEN Brain Science Institute, Saitama, Japan Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai, 201210, China Cited By :5 Export Date: 13 February 2020 Correspondence Address: Csordás, G.; MitoCare Center, Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson UniversityUnited States; email: gyorgy.csordas@jefferson.edu Összes idézések száma a WoS-ban: 0 LA - English DB - MTMT ER - TY - JOUR AU - Martino Adami, Pamela V. AU - Nichtová, Zuzana AU - Weaver, David B. AU - Bartók, Ádám AU - Wisniewski, Thomas AU - Jones, Drew R. AU - Do Carmo, Sonia AU - Castaño, Eduardo M. AU - Cuello, A. Claudio AU - Hajnóczky, György AU - Morelli, Laura TI - Perturbed mitochondria-ER contacts in live neurons that model the amyloid pathology of Alzheimer's disease JF - JOURNAL OF CELL SCIENCE J2 - J CELL SCI VL - 132 PY - 2019 IS - 20 PG - 11 SN - 0021-9533 DO - 10.1242/jcs.229906 UR - https://m2.mtmt.hu/api/publication/30825416 ID - 30825416 LA - English DB - MTMT ER - TY - JOUR AU - Matta, Csaba AU - Juhász, Tamás AU - Fodor, János AU - Hajdú, Tibor AU - Katona, Éva AU - Szucs-Somogyi, Csilla AU - Takács, Roland Ádám AU - Vágó, Judit AU - Oláh, Tamás AU - Bartók, Ádám AU - Varga, Zoltán AU - Panyi, György AU - Csernoch, László AU - Zákány, Róza TI - N-methyl-D-aspartate (NMDA) receptor expression and function is required for early chondrogenesis JF - CELL COMMUNICATION AND SIGNALING J2 - CELL COMM SIGN VL - 17 PY - 2019 IS - 1 PG - 19 SN - 1478-811X DO - 10.1186/s12964-019-0487-3 UR - https://m2.mtmt.hu/api/publication/31015922 ID - 31015922 N1 - 278366 AB - Background: In vitro chondrogenesis depends on the concerted action of numerous signalling pathways, many of which are sensitive to the changes of intracellular Ca2+ concentration. N-methyl-D-aspartate (NMDA) glutamate receptor is a cation channel with high permeability for Ca2+. Whilst there is now accumulating evidence for the expression and function of NMDA receptors in non-neural tissues including mature cartilage and bone, the contribution of glutamate signalling to the regulation of chondrogenesis is yet to be elucidated. Methods: We studied the role of glutamatergic signalling during the course of in vitro chondrogenesis in high density chondrifying cell cultures using single cell fluorescent calcium imaging, patch clamp, transient gene silencing, and western blotting. Results: Here we show that key components of the glutamatergic signalling pathways are functional during in vitro chondrogenesis in a primary chicken chondrogenic model system. We also present the full glutamate receptor subunit mRNA and protein expression profile of these cultures. This is the first study to report that NMDAmediated signalling may act as a key factor in embryonic limb bud-derived chondrogenic cultures as it evokes intracellular Ca2+ transients, which are abolished by the GluN2B subunit-specific inhibitor ifenprodil. The function of NMDARs is essential for chondrogenesis as their functional knock-down using either ifenprodil or GRIN1 siRNA temporarily blocks the differentiation of chondroprogenitor cells. Cartilage formation was fully restored with the reexpression of the GluN1 protein. Conclusions: We propose a key role for NMDARs during the transition of chondroprogenitor cells to cartilage matrix-producing chondroblasts. LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám AU - Paillard, Melanie AU - Debattisti, Valentina AU - Weaver, David AU - Tyburski, Ashley AU - Zhi, Lianteng AU - Zhang, Hui AU - Elliott, Melanie AU - Hajnóczky, György TI - The Role of MICU1 in Neuronal Mitochondrial Calcium Homeostasis and Function JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 112 PY - 2017 IS - 3 SP - 130a EP - 130a PG - 1 SN - 0006-3495 DO - 10.1016/j.bpj.2016.11.723 UR - https://m2.mtmt.hu/api/publication/3312788 ID - 3312788 LA - English DB - MTMT ER - TY - JOUR AU - Fehér, Krisztina AU - Bartók, Ádám AU - Bodor, Andrea AU - Rakosi, K AU - Toth, GK AU - E Kövér, Katalin AU - Panyi, György AU - Varga, Zoltán TI - An engineered peptide toxin analogue with improved Kv1.3 selectivity displays reduced flexibil JF - EUROPEAN BIOPHYSICS JOURNAL J2 - EUR BIOPHYS J VL - 46 PY - 2017 IS - Supplement 1 SP - S214 EP - S214 PG - 1 SN - 0175-7571 UR - https://m2.mtmt.hu/api/publication/3313431 ID - 3313431 LA - English DB - MTMT ER - TY - JOUR AU - Paillard, M AU - Csordás, G AU - Szanda, Gergő AU - Golenár, T AU - Debattisti, V AU - Bartók, Ádám AU - Wang, N AU - Moffat, C AU - Seifert, EL AU - Spät, András AU - Hajnóczky, G TI - Tissue-Specific Mitochondrial Decoding of Cytoplasmic Ca2+ Signals Is Controlled by the Stoichiometry of MICU1/2 and MCU JF - CELL REPORTS J2 - CELL REP VL - 18 PY - 2017 IS - 10 SP - 2291 EP - 2300 PG - 10 SN - 2211-1247 DO - 10.1016/j.celrep.2017.02.032 UR - https://m2.mtmt.hu/api/publication/3201118 ID - 3201118 AB - Mitochondrial Ca2+ uptake through the Ca2+ uniporter supports cell functions, including oxidative metabolism, while meeting tissue-specific calcium signaling patterns and energy needs. The molecular mechanisms underlying tissue-specific control of the uniporter are unknown. Here, we investigated a possible role for tissue-specific stoichiometry between the Ca2+-sensing regulators (MICUs) and pore unit (MCU) of the uniporter. Low MICU1:MCU protein ratio lowered the [Ca2+] threshold for Ca2+ uptake and activation of oxidative metabolism but decreased the cooperativity of uniporter activation in heart and skeletal muscle compared to liver. In MICU1-overexpressing cells, MICU1 was pulled down by MCU proportionally to MICU1 overexpression, suggesting that MICU1:MCU protein ratio directly reflected their association. Overexpressing MICU1 in the heart increased MICU1:MCU ratio, leading to liver-like mitochondrial Ca2+ uptake phenotype and cardiac contractile dysfunction. Thus, the proportion of MICU1-free and MICU1-associated MCU controls these tissue-specific uniporter phenotypes and downstream Ca2+ tuning of oxidative metabolism. © 2017 LA - English DB - MTMT ER - TY - JOUR AU - Paillard, Melanie AU - Csordás, György AU - Szanda, Gergö AU - Golenár, Tünde AU - Debattisti, Valentina AU - Bartók, Ádám AU - Moffat, Cynthia AU - Seifert, Erin L AU - Spät, András AU - Hajnóczky, György TI - Tissue-Specific Mitochondrial Decoding of Cytoplasmic Ca2+ Signals is Controlled by the Stoichiometry of MICU1/2 and MCU JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 112 PY - 2017 IS - 3 SP - 537a EP - 537a PG - 1 SN - 0006-3495 DO - 10.1016/j.bpj.2016.11.2905 UR - https://m2.mtmt.hu/api/publication/3312786 ID - 3312786 LA - English DB - MTMT ER - TY - JOUR AU - Weaver, David AU - Bartók, Ádám AU - Csordas, Gyorgy AU - Hajnoczky, Gyorgy TI - A Standardized Method to Quantify ER-Mitochondrial Interfaces in Electron Mircographs JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 112 PY - 2017 IS - 3 SP - 133a EP - 133a SN - 0006-3495 DO - 10.1016/j.bpj.2016.11.735 UR - https://m2.mtmt.hu/api/publication/3312785 ID - 3312785 LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám AU - Golenár, Tünde AU - Bánsághi, Száva AU - Weaver, David AU - Alzayady, Kamil J AU - Joseph, Suresh K AU - Yule, David I AU - Csordás, György AU - Hajnóczky, György TI - Study of the Capacity of Each IP3 Receptor Isoform to Support ER-Mitochondrial Calcium Transfer JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 110 PY - 2016 IS - 3. Suppl 1 SP - 312a EP - 312a PG - 1 SN - 0006-3495 DO - 10.1016/j.bpj.2015.11.1674 UR - https://m2.mtmt.hu/api/publication/3312787 ID - 3312787 LA - English DB - MTMT ER - TY - JOUR AU - Fehér, Krisztina AU - Timári, István AU - Rákosi, Kinga AU - Szolomájer, János AU - Tóthné Illyés, Tünde Zita AU - Bartók, Ádám AU - Varga, Zoltán AU - Panyi, György AU - Tóth, Gábor AU - E Kövér, Katalin TI - Probing pattern and dynamics of disulfide bridges using synthesis and NMR of an ion channel blocker peptide toxin with multiple diselenide bonds JF - CHEMICAL SCIENCE J2 - CHEM SCI VL - 7 PY - 2016 IS - 4 SP - 2666 EP - 2673 PG - 8 SN - 2041-6520 DO - 10.1039/C5SC03995A UR - https://m2.mtmt.hu/api/publication/2989146 ID - 2989146 N1 - Megjegyzés-27382737 OA gold AB - Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin contg. four disulfide bridges, is a high affinity blocker of the voltage-gated potassium channel Kv1.3, but also blocks Kv1.2. To improve the potential therapeutic use of the toxin, we have designed a double substituted analog, [N17A/F32T]-AnTx, which showed comparable Kv1.3 affinity to the wild-type peptide, but 2500-fold increase in the selectivity for Kv1.3 over Kv1.2. In the present study we have achieved the chem. synthesis of a Sec-analog in which all cysteine (Cys) residues have been replaced by selenocysteine (Sec) forming four diselenide bonds. To the best of our knowledge this is the first time to replace, by chem. synthesis, all disulfide bonds with isosteric diselenides in a peptide/protein. Gratifyingly, the key pharmacol. properties of the Sec-[N17A/F32T]-AnTx are retained since the peptide is functionally active. We also propose here a combined exptl. and theor. approach including NOE- and 77Se-based NMR supplemented by MD simulations for conformational and dynamic characterization of the Sec-[N17A/F32T]-AnTx. The use of such combined approach allowed us to attain unequivocal assignment of all four diselenide bonds and supplemental MD simulations allowed to characterize the conformational dynamics around each disulfide/diselenide bridge. [on SciFinder(R)] LA - English DB - MTMT ER - TY - JOUR AU - Olamendi-Portugal, T AU - Bartók, Ádám AU - Zamudio-Zuniga, F AU - Balajthy, András AU - Becerril, B AU - Panyi, György AU - Possani, L D TI - Isolation, chemical and functional characterization of several new K+-channel blocking peptides from the venom of the scorpion Centruroides tecomanus JF - TOXICON J2 - TOXICON VL - 115 PY - 2016 SP - 1 EP - 12 PG - 12 SN - 0041-0101 DO - 10.1016/j.toxicon.2016.02.017 UR - https://m2.mtmt.hu/api/publication/3032713 ID - 3032713 N1 - Olamendi-Portugal T. and Bartok A. contributed equally to the manuscript. AB - Six new peptides were isolated from the venom of the Mexican scorpion Centruroides tecomanus; their primary structures were determined and the effects on ion channels were verified by patch-clamp experiments. Four are K+-channel blockers of the alpha-KTx family, containing 32 to 39 amino acid residues, cross-linked by three disulfide bonds. They all block Kv1.2 in nanomolar concentrations and show various degree of selectivity over Kv1.1, Kv1.3, Shaker and KCa3.1 channels. One peptide has 42 amino acids cross-linked by four disulfides; it blocks ERG-channels and belongs to the gamma-KTx family. The sixth peptide has only 32 amino acid residues, three disulfide bonds and has no effect on the ion-channels assayed. It also does not have antimicrobial activity. Systematic numbers were assigned (time of elution on HPLC): alpha-KTx 10.4 (time 24.1); alpha-KTx 2.15 (time 26.2); alpha-KTx 2.16 (time 23.8); alpha-KTx 2.17 (time 26.7) and gamma-KTx 1.9 (elution time 29.6). A partial proteomic analysis of the short chain basic peptides of this venom, which elutes on carboxy-methyl-cellulose column fractionation, is included. The pharmacological properties of the peptides described in this study may provide valuable tools for understanding the structure-function relationship of K+ channel blocking scorpion toxins. LA - English DB - MTMT ER - TY - JOUR AU - Pethő, Zoltán Dénes AU - Balajthy, András AU - Bartók, Ádám AU - Bene, Krisztián AU - Somodi, Sándor AU - Szilagyi, O AU - Rajnavölgyi, Éva AU - Panyi, György AU - Varga, Zoltán TI - The anti-proliferative effect of cation channel blockers in T lymphocytes depends on the strength of mitogenic stimulation JF - IMMUNOLOGY LETTERS J2 - IMMUNOL LETT VL - 171 PY - 2016 SP - 60 EP - 69 PG - 10 SN - 0165-2478 DO - 10.1016/j.imlet.2016.02.003 UR - https://m2.mtmt.hu/api/publication/3023306 ID - 3023306 AB - Ion channels are crucially important for the activation and proliferation of T lymphocytes, and thus, for the function of the immune system. Previous studies on the effects of channel blockers on T cell proliferation reported variable effectiveness due to differing experimental systems. Therefore our aim was to investigate how the strength of the mitogenic stimulation influences the efficiency of cation channel blockers in inhibiting activation, cytokine secretion and proliferation of T cells under standardized conditions. Human peripheral blood lymphocytes were activated via monoclonal antibodies targeting the TCR-CD3 complex and the co-stimulator CD28. We applied the blockers of Kv1.3 (Anuroctoxin), KCa3.1 (TRAM- 34) and CRAC (2-Apb) channels of T cells either alone or in combination with rapamycin, the inhibitor of the mammalian target of rapamycin (mTOR). Five days after the stimulation ELISA and flow cytometric measurements were performed to determine IL-10 and IFN- secretion, cellular viability and proliferation. Our results showed that ion channel blockers and rapamycin inhibit IL-10 and IFN- secretion and cell division in a dose-dependent manner. Simultaneous application of the blockers for each channel along with rapamycin was the most effective, indicating synergy among the various activation pathways. Upon increasing the extent of mitogenic stimulation the anti- proliferative effect of the ion channel blockers diminished. This phenomenon may be important in understanding the fine-tuning of T cell activation. © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved. LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám AU - Fehér, Krisztina AU - Bodor, Andrea AU - Rákosi, Kinga AU - Tóth, Gábor AU - E Kövér, Katalin AU - Panyi, György AU - Varga, Zoltán TI - An engineered scorpion toxin analogue with improved Kv1.3 selectivity displays reduced conformational flexibility. JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 5 PY - 2015 PG - 13 SN - 2045-2322 DO - 10.1038/srep18397 UR - https://m2.mtmt.hu/api/publication/2989144 ID - 2989144 AB - The voltage-gated Kv1.3 K(+) channel plays a key role in the activation of T lymphocytes. Kv1.3 blockers selectively suppress immune responses mediated by effector memory T cells, which indicates the great potential of selective Kv1.3 inhibitors in the therapy of certain autoimmune diseases. Anuroctoxin (AnTx), a 35-amino-acid scorpion toxin is a high affinity blocker of Kv1.3, but also blocks Kv1.2 with similar potency. We designed and produced three AnTx variants: ([F32T]-AnTx, [N17A]-AnTx, [N17A/F32T]-AnTx) using solid-phase synthesis with the goal of improving the selectivity of the toxin for Kv1.3 over Kv1.2 while keeping the high affinity for Kv1.3. We used the patch-clamp technique to determine the blocking potency of the synthetic toxins on hKv1.3, mKv1.1, hKv1.2 and hKCa3.1 channels. Of the three variants [N17A/F32T]-AnTx maintained the high affinity of the natural peptide for Kv1.3 but became more than 16000-fold selective over Kv1.2. NMR data and molecular dynamics simulations suggest that the more rigid structure with restricted conformational space of the double substituted toxin compared to the flexible wild-type one is an important determinant of toxin selectivity. Our results provide the foundation for the possibility of the production and future therapeutic application of additional, even more selective toxins targeting various ion channels. LA - English DB - MTMT ER - TY - CHAP AU - Bartók, Ádám AU - Panyi, György AU - Varga, Zoltán ED - Gopalakrishnakone, P ED - Ferroni, Schwartz Elisabeth ED - Possani, Lourival D ED - Rodríguez, de la Vega Ricardo C TI - Potassium Channel Blocking Peptide Toxins from Scorpion Venom T2 - Scorpion Venoms PB - Springer Netherlands CY - Dordrecht PY - 2015 SP - 493 EP - 527 PG - 35 DO - 10.1007/978-94-007-6404-0_30 UR - https://m2.mtmt.hu/api/publication/2781106 ID - 2781106 N1 - Cited By :10 Export Date: 4 May 2023 Correspondence Address: Bartok, A.; Department of Biophysics and Cell Biology, University of DebrecenHungary LA - English DB - MTMT ER - TY - JOUR AU - Varga, Zoltán AU - Pethő, Zoltán Dénes AU - Balajthy, András AU - Bartók, Ádám AU - Somodi, Sándor AU - Szilágyi, Orsolya AU - Panyi, György TI - The Anti-Proliferative Effect of Cation Channel Blockers on T Lymphocytes Stimulated by Anti-CD3 and Anti-CD28 JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 108 PY - 2015 IS - 2 SP - 586a EP - 587a SN - 0006-3495 DO - 10.1016/j.bpj.2014.11.3199 UR - https://m2.mtmt.hu/api/publication/3338294 ID - 3338294 N1 - Document Type:Meeting Abstract Biophysical Journal # Kezdő dátum ismeretlen # Ország ismeretlen # Város ismeretlen WoS:hiba:000362849600570 2020-08-29 22:50 típus nem egyezik AB - Meeting Abstract: 2962-Pos LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám AU - Tóth, Ágnes AU - Somodi, Sándor AU - Szántó, Gábor Tibor AU - Hajdu, Péter Béla AU - Panyi, György AU - Varga, Zoltán TI - Margatoxin is a non-selective inhibitor of human Kv1.3 K+ channels. JF - TOXICON J2 - TOXICON VL - 87 PY - 2014 SP - 6 EP - 16 PG - 11 SN - 0041-0101 DO - 10.1016/j.toxicon.2014.05.002 UR - https://m2.mtmt.hu/api/publication/2725004 ID - 2725004 AB - Margatoxin (MgTx), an alpha-KTx scorpion toxin, is considered a selective inhibitor of the Kv1.3K + channel. This peptide is widely used in ion channel research; however, a comprehensive study of its selectivity with electrophysiological methods has not been published yet. The lack of selectivity might lead to undesired side effects upon therapeutic application or may lead to incorrect conclusion regarding the role of a particular ion channel in a physiological or pathophysiological response either in vitro or in vivo. Using the patch-clamp technique we characterized the selectivity profile of MgTx using L929 cells expressing mKv1.1 channels, human peripheral lymphocytes expressing Kv1.3 channels and transiently transfected tsA201 cells expressing hKv1.1, hKv1.2, hKv1.3, hKv1.4-IR, hKv1.5, hKv1.6, hKv1.7, rKv2.1, Shaker-IR, hERG, hKCa1.1, hKCa3.1 and hNav1.5 channels. MgTx is indeed a high affinity inhibitor of Kv1.3 (Kd = 11.7 pM) but is not selective, it inhibits the Kv1.2 channel with similar affinity (Kd = 6.4 pM) and Kv1.1 in the nanomolar range (Kd = 4.2 nM). Based on our comprehensive data MgTX has to be considered a non-selective Kv1.3 inhibitor, and thus, experiments aiming at elucidating the significance of Kv1.3 in in vitro or in vivo physiological responses have to be carefully evaluated. LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám AU - Tóth, Ágnes AU - Hajdu, Péter Béla AU - Varga, Zoltán AU - Panyi, György TI - Margatoxin is a Nonselective Inhibitor of Kv1.3 Channels - A Comprehensive Study JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 106 PY - 2014 IS - 2 SU 1 SP - 551A EP - 552A SN - 0006-3495 DO - 10.1016/j.bpj.2013.11.3070 UR - https://m2.mtmt.hu/api/publication/2773131 ID - 2773131 N1 - WoS:hiba:000337000403134 2019-09-11 13:39 füzet nem egyezik LA - English DB - MTMT ER - TY - THES AU - Bartók, Ádám TI - Kv1.3 csatorna-gátló skorpiótoxinok farmakológiai vizsgálata PY - 2014 SP - 95 UR - https://m2.mtmt.hu/api/publication/2974046 ID - 2974046 N1 - Az angol nyelvű tézisben megadott cím: Pharmacological characterization of Kv1.3 inhibitor scorpion toxins LA - English DB - MTMT ER - TY - JOUR AU - Luna-Ramirez, K AU - Bartók, Ádám AU - Restano-Cassulini, R AU - Quintero-Hernandez, V AU - Coronas, FI AU - Christensen, J AU - Wright, CE AU - Panyi, György AU - Possani, LD TI - Structure, Molecular Modeling, and Function of the Novel Potassium Channel Blocker Urotoxin Isolated from the Venom of the Australian Scorpion Urodacus yaschenkoi. JF - MOLECULAR PHARMACOLOGY J2 - MOL PHARMACOL VL - 86 PY - 2014 IS - 1 SP - 28 EP - 41 PG - 14 SN - 0026-895X DO - 10.1124/mol.113.090183 UR - https://m2.mtmt.hu/api/publication/2590521 ID - 2590521 AB - This communication reports the structural and functional characterization of urotoxin, the first K(+) channel toxin isolated from the venom of the Australian scorpion Urodacus yaschenkoi. It is a basic peptide consisting of 37 amino acids with an amidated C-terminal residue. Urotoxin contains eight cysteines forming four disulfide bridges with sequence similarities resembling the alpha-potassium channel toxin 6 (alpha-KTx-6) subfamily of peptides; it was assigned the systematic number of alpha-KTx-6.21. Urotoxin is a potent blocker of human voltage-gated potassium channel (Kv)1.2 channels, with an IC50 of 160 pM, whereas its affinity for other channels tested was in the nanomolar range (hKv1.1, IC50 = 253 nM; hKv1.3, IC50 = 91 nM; and hKCa3.1, IC50 = 70 nM). The toxin had no effect on hKv1.4, hKv1.5, human ether-a-go-go-related gene type 1 (hERG1), or human ether-a-go-go-like (hELK2) channels. Multiple sequence alignments from the venom gland transcriptome showed the existence of four other new peptides similar to urotoxin. Computer modeling of urotoxin's three-dimensional structure suggests the presence of the alpha/beta-scaffold characteristic of other scorpion toxins, although very likely forming an uncommon disulfide pairing pattern. Using molecular dynamics, a model for the binding of this peptide to human Kv1.2 and hKv1.1 channels is presented, along with the binding of an in silico mutant urotoxin (Lys25Ala) to both channels. Urotoxin enriches our knowledge of K(+) channel toxins and, due to its high affinity for hKv1.2 channels, it may be a good candidate for the development of pharmacologic tools to study the physiologic functions of K(+) channels or related channelopathies and for restoring axonal conduction in demyelinated axons. LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám AU - Panyi, György AU - Possani, LD AU - Varga, Zoltán TI - Molecular Determinants of Selectivity for Kv1.3 K+ Channels JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 104 PY - 2013 IS - 2 SU 1 SP - 465A EP - 465A SN - 0006-3495 DO - 10.1016/j.bpj.2012.11.2572 UR - https://m2.mtmt.hu/api/publication/2360449 ID - 2360449 N1 - CT 57th Annual Meeting of the Biophysical-Society CY FEB 02-06, 2013 CL Philadelphia, PA SU 1 LA - English DB - MTMT ER - TY - JOUR AU - Schwartz, EF AU - Bartók, Ádám AU - Schwartz, CA AU - Papp, Ferenc AU - Gomez-Lagunas, F AU - Panyi, György AU - Possani, LD TI - OcyKTx2, a new K+-channel toxin characterized from the venom of the scorpion Opisthacanthus cayaporum JF - PEPTIDES J2 - PEPTIDES VL - 46 PY - 2013 SP - 40 EP - 46 PG - 7 SN - 0196-9781 DO - 10.1016/j.peptides.2013.04.021 UR - https://m2.mtmt.hu/api/publication/2394156 ID - 2394156 AB - Opisthacanthus cayaporum belongs to the Liochelidae family, and the scorpions from this genus occur in southern Africa, Central America and South America and, therefore, can be considered a true Gondwana heritage. In this communication, the isolation, primary structure characterization, and K(+)-channel blocking activity of new peptide from this scorpion venom are reported. OcyKTx2 is a 34 amino acid long peptide with four disulfide bridges and molecular mass of 3807Da. Electrophysiological assays conducted with pure OcyKTx2 showed that this toxin reversibly blocks Shaker B K(+)-channels with a Kd of 82nM, and presents an even better affinity toward hKv1.3, blocking it with a Kd of approximately 18nM. OcyKTx2 shares high sequence identity with peptides belonging to subfamily 6 of alpha-KTxs that clustered very closely in the phylogenetic tree included here. Sequence comparison, chain length and number of disulfide bridges analysis classify OcyKTx2 into subfamily 6 of the alpha-KTx scorpion toxins (systematic name, alpha-KTx6.17). LA - English DB - MTMT ER - TY - JOUR AU - Szentandrássy, Norbert AU - Papp, Ferenc AU - Hegyi, Bence AU - Bartók, Ádám AU - Krasznai, Zoltán AU - Nánási, Péter Pál TI - Tetrodotoxin blocks native cardiac L-type calcium channels but not CaV1.2 channels expressed in HEK cells. JF - JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY J2 - J PHYSIOL PHARMACOL VL - 64 PY - 2013 IS - 6 SP - 807 EP - 810 PG - 4 SN - 0867-5910 UR - https://m2.mtmt.hu/api/publication/2502508 ID - 2502508 N1 - Összes idézések száma a WoS-ban: 0 AB - Tetrodotoxin (TTX) has been believed for a long time to be a selective inhibitor of voltage-gated fast Na(+) channels in excitable tissues, including mammalian myocardium. Recently TTX has been shown to block cardiac L-type Ca(2+) current (ICa,L). Furthermore, this inhibition was ascribed to binding of TTX to the outer pore of the Ca(2+) channel, contributing to the selectivity filter region. In this study the TTX-sensitivity of Cav1.2 channels, expressed in HEK cells, was tested using the whole cell version of the patch clamp technique and compared to the TTX-sensitivity of native canine ICa,L. Cav1.2 channels mediate Ca(2+) current in ventricular myocardium of various mammalian species. Surprisingly, TTX failed to inhibit Cav1.2 current up to the concentration of 100 muM - in contrast to ICa,L - in spite of the fact that the kinetic properties of the ICa,L and Cav1.2 currents were similar. The possible reasons for this discrepancy are discussed. Present results may question the suitability of a single pore-forming channel subunit, expressed in a transfection system, for electrophysiological or pharmacological studies. LA - English DB - MTMT ER - TY - JOUR AU - Bartók, Ádám AU - Varga, Zoltán AU - Panyi, György TI - Tailoring the Selectivity of Anuroctoxin for Kv1.3 K+ Channels JF - TOXICON J2 - TOXICON VL - 60 PY - 2012 IS - 2 SP - 171 EP - 172 PG - 2 SN - 0041-0101 DO - 10.1016/j.toxicon.2012.04.151 UR - https://m2.mtmt.hu/api/publication/2032613 ID - 2032613 N1 - CT 17th World Congress of the International-Society-on-Toxinology (IST)/Venom Week/4th International Scientific Symposium on All Things Venomous CY JUL 08-13, 2012 CL Honolulu, HI LA - English DB - MTMT ER - TY - JOUR AU - Varga, Zoltán AU - Juhász, Tamás AU - Matta, Csaba AU - Fodor, János AU - Katona, Éva AU - Bartók, Ádám AU - Oláh, Tamás AU - Sebe, A. AU - Csernoch, László AU - Panyi, György AU - Zákány, Róza TI - Switch of Voltage-Gated K+ Channel Expression in the Plasma Membrane of Chondrogenic Cells Affects Cytosolic Ca2+-Oscillations and Cartilage Formation JF - PLOS ONE J2 - PLOS ONE VL - 6 PY - 2011 IS - 11 SN - 1932-6203 DO - 10.1371/journal.pone.0027957 UR - https://m2.mtmt.hu/api/publication/32014676 ID - 32014676 N1 - Department of Biophysics and Cell Biology, University of Debrecen Medical and Health Science Center, Debrecen, Hungary Department of Anatomy, Histology and Embryology, University of Debrecen Medical and Health Science Center, Debrecen, Hungary Department of Physiology, University of Debrecen Medical and Health Science Center, Debrecen, Hungary Correspondence Address: Panyi, G.; Department of Biophysics and Cell Biology, , Debrecen, Hungary; email: panyi@med.unideb.hu AB - Background: Understanding the key elements of signaling of chondroprogenitor cells at the earliest steps of differentiation may substantially improve our opportunities for the application of mesenchymal stem cells in cartilage tissue engineering, which is a promising approach of regenerative therapy of joint diseases. Ion channels, membrane potential and Ca 2+-signaling are important regulators of cell proliferation and differentiation. Our aim was to identify such plasma membrane ion channels involved in signaling during chondrogenesis, which may serve as specific molecular targets for influencing chondrogenic differentiation and ultimately cartilage formation. Methodology/Principal Findings: Using patch-clamp, RT-PCR and Western-blot experiments, we found that chondrogenic cells in primary micromass cell cultures obtained from embryonic chicken limb buds expressed voltage-gated Na V1.4, K V1.1, K V1.3 and K V4.1 channels, although K V1.3 was not detectable in the plasma membrane. Tetrodotoxin (TTX), the inhibitor of Na V1.4 channels, had no effect on cartilage formation. In contrast, presence of 20 mM of the K + channel blocker tetraethyl-ammonium (TEA) during the time-window of the final commitment of chondrogenic cells reduced K V currents (to 27±3% of control), cell proliferation (thymidine incorporation: to 39±4.4% of control), expression of cartilage-specific genes and consequently, cartilage formation (metachromasia: to 18.0±6.4% of control) and also depolarized the membrane potential (by 9.3±2.1 mV). High-frequency Ca 2+-oscillations were also suppressed by 10 mM TEA (confocal microscopy: frequency to 8.5±2.6% of the control). Peak expression of TEA-sensitive K V1.1 in the plasma membrane overlapped with this period. Application of TEA to differentiated chondrocytes, mainly expressing the TEA-insensitive K V4.1 did not affect cartilage formation. Conclusions/Significance: These data demonstrate that the differentiation and proliferation of chondrogenic cells depend on rapid Ca 2+-oscillations, which are modulated by K V-driven membrane potential changes. K V1.1 function seems especially critical during the final commitment period. We show the critical role of voltage-gated cation channels in the differentiation of non-excitable cells with potential therapeutic use. © 2011 Varga et al. LA - English DB - MTMT ER - TY - JOUR AU - Varga, Zoltán AU - Bartók, Ádám AU - Panyi, György AU - Zákány, Róza AU - Juhász, Tamás AU - Matta, Csaba AU - Fodor, János AU - Dienes, Beatrix AU - Csernoch, László TI - Voltage-Gated Ion Channels are Involved in the Signaling Pathway of Differentiating Chondrocytes JF - BIOPHYSICAL JOURNAL J2 - BIOPHYS J VL - 100 PY - 2011 IS - 3 Supplement 1 SP - 93a EP - 93a PG - 1 SN - 0006-3495 DO - 10.1016/j.bpj.2010.12.712 UR - https://m2.mtmt.hu/api/publication/2507777 ID - 2507777 LA - English DB - MTMT ER -