TY - JOUR AU - Horváth, Ádám AU - Steib, Anita AU - Nehr-Majoros, Andrea Kinga AU - Kántás, Boglárka AU - Király, Ágnes AU - Racskó, Márk AU - Tóth, Balázs István AU - Szánti-Pintér, Eszter AU - Kudová, Eva AU - Skodáné Földes, Rita AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Anti-Nociceptive Effects of Sphingomyelinase and Methyl-Beta-Cyclodextrin in the Icilin-Induced Mouse Pain Model JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 9 PG - 13 SN - 1661-6596 DO - 10.3390/ijms25094637 UR - https://m2.mtmt.hu/api/publication/34824919 ID - 34824919 AB - The thermo- and pain-sensitive Transient Receptor Potential Melastatin 3 and 8 (TRPM3 and TRPM8) ion channels are functionally associated in the lipid rafts of the plasma membrane. We have already described that cholesterol and sphingomyelin depletion, or inhibition of sphingolipid biosynthesis decreased the TRPM8 but not the TRPM3 channel opening on cultured sensory neurons. We aimed to test the effects of lipid raft disruptors on channel activation on TRPM3- and TRPM8-expressing HEK293T cells in vitro, as well as their potential analgesic actions in TRPM3 and TRPM8 channel activation involving acute pain models in mice. CHO cell viability was examined after lipid raft disruptor treatments and their effects on channel activation on channel expressing HEK293T cells by measurement of cytoplasmic Ca2+ concentration were monitored. The effects of treatments were investigated in Pregnenolone-Sulphate-CIM-0216-evoked and icilin-induced acute nocifensive pain models in mice. Cholesterol depletion decreased CHO cell viability. Sphingomyelinase and methyl-beta-cyclodextrin reduced the duration of icilin-evoked nocifensive behavior, while lipid raft disruptors did not inhibit the activity of recombinant TRPM3 and TRPM8. We conclude that depletion of sphingomyelin or cholesterol from rafts can modulate the function of native TRPM8 receptors. Furthermore, sphingolipid cleavage provided superiority over cholesterol depletion, and this method can open novel possibilities in the management of different pain conditions. LA - English DB - MTMT ER - TY - JOUR AU - Hudhud, Lina AU - Kovács-Rozmer, Katalin AU - Kecskés, Angéla AU - Pohóczky, Krisztina AU - Bencze, Noémi AU - Buzás, Krisztina AU - Szőke, Éva AU - Helyes, Zsuzsanna TI - Transient Receptor Potential Ankyrin 1 Ion Channel Is Expressed in Osteosarcoma and Its Activation Reduces Viability JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 25 PY - 2024 IS - 7 PG - 13 SN - 1661-6596 DO - 10.3390/ijms25073760 UR - https://m2.mtmt.hu/api/publication/34797924 ID - 34797924 N1 - * Megosztott szerzőség AB - Osteosarcoma is a highly malignant, painful cancer with poor treatment opportunities and a bad prognosis. Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are non-selective cation channels that have been of great interest in cancer, as their expression is increased in some malignancies. In our study we aim to characterize the expression and functionality of the TRPA1 and TRPV1 channels in human and mouse osteosarcoma tissues and in a mouse cell line. TRPA1/Trpa1 and TRPV1/Trpv1 mRNA expressions were demonstrated by PCR gel electrophoresis and RNAscope in situ hybridization. The function of these channels was confirmed by their radioactive 45Ca2+ uptake in response to the TRPA1 agonist, Allyl-isothiocyanate (AITC), and TRPV1 agonist, capsaicin, in K7M2 cells. An ATP-based K2M7 cell viability luminescence assay was used to determine cell viability after AITC or capsaicin treatments. Both TRPA1/Trpa1 and TRPV1/Trpv1 were expressed similarly in human and mouse osteosarcoma tissues, while Trpa1 transcripts were more abundantly present in K7M2 cells. TRPA1 activation with 200 µM AITC induced a significant 45Ca2+ influx into K7M2 cells, and the antagonist attenuated this effect. In accordance with the lower Trpv1 expression, capsaicin induced a moderate 45Ca2+ uptake, which did not reach the level of statistical significance. Both AITC and capsaicin significantly reduced K7M2 cell viability, demonstrating EC50 values of 22 µM and 74 µM. The viability-decreasing effect of AITC was significantly but only partially antagonized by HC-030031, but the action of capsaicin was not affected by the TRPV1 antagonist capsazepine. We provide here the first data on the functional expression of the TRPA1 and TRPV1 ion channels in osteosarcoma, suggesting novel diagnostic and/or therapeutic perspectives. LA - English DB - MTMT ER - TY - JOUR AU - Poór, Miklós AU - Dombi, Ágnes AU - Fliszár-Nyúl, Eszter AU - Pedroni, Lorenzo AU - Dellafiora, Luca TI - Effects of Chrysin and Chrysin-7-sulfate on Ochratoxin A-Albumin Interactions and on the Plasma and Kidney Levels of the Mycotoxin in Rats JF - ACS OMEGA J2 - ACS OMEGA VL - 9 PY - 2024 IS - 15 SP - 17655 EP - 17666 PG - 12 SN - 2470-1343 DO - 10.1021/acsomega.4c01738 UR - https://m2.mtmt.hu/api/publication/34766036 ID - 34766036 N1 - Department of Laboratory Medicine, Medical School, University of Pécs, Ifjúság útja 13, Pécs, H-7624, Hungary Molecular Medicine Research Group, János Szentágothai Research Centre, University of Pécs, Ifjúság útja 20, Pécs, H-7624, Hungary Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus u. 2, Pécs, H-7624, Hungary Department of Food and Drug, University of Parma, Via G.P. Usberti 27/A, Parma, 43124, Italy Export Date: 3 May 2024 Correspondence Address: Poór, M.; Department of Laboratory Medicine, Ifjúság útja 13, Hungary; email: poor.miklos@pte.hu LA - English DB - MTMT ER - TY - JOUR AU - Kaci, Hana AU - Bakos, Éva AU - Needs, Paul W. AU - Kroon, Paul A. AU - Valentová, Kateřina AU - Poór, Miklós AU - Laczka, Csilla TI - The 2-aminoethyl diphenylborinate-based fluorescent method identifies quercetin and luteolin metabolites as substrates of Organic anion transporting polypeptides, OATP1B1 and OATP2B1 JF - EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES J2 - EUR J PHARM SCI PY - 2024 SN - 0928-0987 DO - 10.1016/j.ejps.2024.106740 UR - https://m2.mtmt.hu/api/publication/34719089 ID - 34719089 AB - Organic anion transporting polypeptides (OATPs), OATP1B1 and OATP2B1 are membrane proteins mediating the cellular uptake of chemically diverse organic compounds. OATP1B1 is exclusively expressed in hepatocytes and plays a key role in hepatic detoxification. The ubiquitously expressed OATP2B1 promotes the intestinal absorption of orally administered drugs. Flavonoids are widely found in foods and beverages, and many of them can inhibit OATP function, resulting in food-drug interactions. In our previous work, we have shown that not only luteolin (LUT) and quercetin (Q), but also some of their metabolites can inhibit OATP1B1 and OATP2B1 activity. However, data about the potential direct transport of these flavonoids by OATPs have been incomplete. Hence, in the current study, we developed a simple, fluorescence-based method for the measurement of intracellular flavonoid levels. The method applies a cell-permeable small molecule (2-aminoethyl diphenylborinate, 2-APB), that, upon forming a complex with flavonoids, results in their fluorescence enhancement. This way the direct uptake of LUT and Q, and also their metabolites could be investigated both by confocal microscopy and in a fluorescence plate reader in living cells. With this approach we identified quercetin-3'-O-sulfate, luteolin-3'-O-glucuronide, luteolin-7-O-glucuronide and luteolin-3'-O-sulfate as substrates of both OATP1B1 and OATP2B1. Our results highlight that OATP1B1 and OATP2B1 can be key participants in the transmembrane movement of cell-permeable LUT and Q conjugates with otherwise low cell permeability. In addition, the novel method developed in this study can be a good completion to existing fluorescence-based assays to investigate OATP function. LA - English DB - MTMT ER - TY - JOUR AU - Pethő, Gábor AU - Kántás, Boglárka AU - Horváth, Ádám AU - Pintér, Erika TI - The Epigenetics of Neuropathic Pain: A Systematic Update JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 24 PY - 2023 IS - 24 PG - 32 SN - 1661-6596 DO - 10.3390/ijms242417143 UR - https://m2.mtmt.hu/api/publication/34424543 ID - 34424543 N1 - Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti Str. 12., Pécs, H-7624, Hungary Department of Pharmacology, Faculty of Pharmacy, University of Pécs, Rókus Str. 2, Pécs, H-7624, Hungary Department of Obstetrics and Gynecology, University of Pécs, Édesanyák Str. 17, Pécs, H-7624, Hungary Export Date: 8 January 2024 Correspondence Address: Pethő, G.; Department of Pharmacology and Pharmacotherapy, Szigeti Str. 12., Hungary; email: gabor.petho@aok.pte.hu AB - Epigenetics deals with alterations to the gene expression that occur without change in the nucleotide sequence in the DNA. Various covalent modifications of the DNA and/or the surrounding histone proteins have been revealed, including DNA methylation, histone acetylation, and methylation, which can either stimulate or inhibit protein expression at the transcriptional level. In the past decade, an exponentially increasing amount of data has been published on the association between epigenetic changes and the pathomechanism of pain, including its most challenging form, neuropathic pain. Epigenetic regulation of the chromatin by writer, reader, and eraser proteins has been revealed for diverse protein targets involved in the pathomechanism of neuropathic pain. They include receptors, ion channels, transporters, enzymes, cytokines, chemokines, growth factors, inflammasome proteins, etc. Most work has been invested in clarifying the epigenetic downregulation of mu opioid receptors and various K+ channels, two types of structures mediating neuronal inhibition. Conversely, epigenetic upregulation has been revealed for glutamate receptors, growth factors, and lymphokines involved in neuronal excitation. All these data cannot only help better understand the development of neuropathic pain but outline epigenetic writers, readers, and erasers whose pharmacological inhibition may represent a novel option in the treatment of pain. LA - English DB - MTMT ER - TY - JOUR AU - van Eijk, Nicholas AU - Schmacke, Luna C. AU - Steinmetzer, Torsten AU - Pilgram, Oliver AU - Poór, Miklós AU - Pásztiné Gere, Erzsébet TI - In vitro testing of host-targeting small molecule antiviral matriptase/TMPRSS2 inhibitors in 2D and 3D cell-based assays JF - BIOMEDICINE & PHARMACOTHERAPY J2 - BIOMED PHARMACOTHER VL - 168 PY - 2023 PG - 13 SN - 0753-3322 DO - 10.1016/j.biopha.2023.115761 UR - https://m2.mtmt.hu/api/publication/34213742 ID - 34213742 N1 - A szerzők egyike hallgató Funding text: Project no. RRF-2.3.1-21-2022-00001 has been implemented with the support provided by the Recovery and Resilience Facility (RRF) , financed under the National Recovery Fund budget estimate, RRF-2.3.1-21 funding scheme. The work of M.P. was supported by the UNKP-22-5 New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, Development and Innovation Fund. This project was supported by under grant number This study was supported by the strategic research fund of the University of Veterinary Medicine Budapest (Grant No. SRF-001.) . LA - English DB - MTMT ER - TY - JOUR AU - Toth, Norbert AU - Hogden, Marthe Gjerstad AU - Szoke, Eva AU - Helyes, Zsuzsanna AU - Pohóczky, Krisztina TI - Expression and function of the Transient Receptor Vanilloid 1 and Ankyrin 1 ion channels in endometriosis cell line JF - BRITISH JOURNAL OF PHARMACOLOGY J2 - BR J PHARMACOL VL - 180 PY - 2023 SP - 766 EP - 767 PG - 2 SN - 0007-1188 UR - https://m2.mtmt.hu/api/publication/34212259 ID - 34212259 LA - English DB - MTMT ER - TY - JOUR AU - Balázs, Orsolya AU - Dombi, Ágnes AU - Zsidó, Balázs Zoltán AU - Hetényi, Csaba AU - Valentová, Kateřina AU - Vida, Róbert György AU - Poór, Miklós TI - Inhibition of xanthine oxidase-catalyzed xanthine and 6-mercaptopurine oxidation by luteolin, naringenin, myricetin, ampelopsin and their conjugated metabolites. JF - BIOMEDICINE & PHARMACOTHERAPY J2 - BIOMED PHARMACOTHER VL - 167 PY - 2023 PG - 10 SN - 0753-3322 DO - 10.1016/j.biopha.2023.115548 UR - https://m2.mtmt.hu/api/publication/34153929 ID - 34153929 N1 - Funding Agency and Grant Number: Hungarian National Research, Development and Innovation Office [FK138184]; Hungarian Academy of Sciences [BO/00381/21]; Czech Science Foundation [23-04654S]; PTE; European Union - European Social Fund [AOK KA-2022-26]; [EFOP-3.6.1-16-2016-00004] Funding text: The work of M.P. is supported by the Hungarian National Research, Development and Innovation Office (FK138184) and by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00381/21) . K.V. was supported by Czech Science Foundation (23-04654S) . The project has been supported the PTE AOK KA-2022-26 grant, and by the European Union, co-financed by the European Social Fund (project name and code: Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs, EFOP-3.6.1-16-2016-00004) . AB - Luteolin, naringenin, myricetin, and ampelopsin are abundant flavonoids in nature, and several dietary supplements also contain them at very high doses. After the peroral intake, flavonoids go through extensive presystemic biotransformation; therefore, typically their sulfate/glucuronic acid conjugates reach high concentrations in the circulation. Xanthine oxidase (XO) enzyme is involved in uric acid production, and it also takes part in the elimination of certain drugs (e.g., 6-mercaptopurine). The inhibitory effects of flavonoid aglycones on XO have been widely studied; however, only limited data are available regarding their sulfate and glucuronic acid conjugates. In this study, we examined the impacts of luteolin, naringenin, myricetin, ampelopsin, and their sulfate/glucuronide derivatives on XO-catalyzed xanthine and 6-mercaptopurine oxidations employing in vitro enzyme incubation assays and molecular modeling studies. Our major results/conclusions are the following: (1) Sulfate metabolites were stronger while glucuronic acid derivatives were weaker inhibitors of XO compared to the parent flavonoids. (2) Naringenin, ampelopsin, and their metabolites were weak inhibitors of the enzyme. (3) Luteolin, myricetin, and their sulfates were highly potent inhibitors of XO, and the glucuronides of luteolin showed moderate inhibitory impacts. (4) Conjugated metabolites of luteolin and myricetin can be involved in the inhibitory effects of these flavonoids on XO enzyme. LA - English DB - MTMT ER - TY - JOUR AU - Hlogyik, Tamás AU - Laczkó-Rigó, Réka AU - Bakos, Éva AU - Poór, Miklós AU - Kele, Zoltán AU - Laczka, Csilla AU - Mernyák, Erzsébet TI - Synthesis and in vitro photodynamic activity of aza-BODIPY-based photosensitizers JF - ORGANIC & BIOMOLECULAR CHEMISTRY J2 - ORG BIOMOL CHEM VL - 21 PY - 2023 IS - 29 SP - 6018 EP - 6027 PG - 10 SN - 1477-0520 DO - 10.1039/d3ob00699a UR - https://m2.mtmt.hu/api/publication/34067941 ID - 34067941 N1 - * Megosztott szerzőség AB - Aza-BODIPY dyes have recently come to attention owing to their excellent chemical and photophysical properties. In particular, their absorption and emission maxima can efficiently be shifted to the red or even to the NIR spectral region. On this basis, aza-BODIPY derivatives are widely investigated as fluorescent probes or phototherapeutic agents. Here we report the synthesis of a set of novel aza-BODIPY derivatives as potential photosensitizers for use in photodynamic therapy. Triazolyl derivatives were obtained via Cu(I)-catalyzed azide-alkyne cycloaddition as the key step. In vitro photodynamic activities of the newly synthesized compounds were evaluated on the A431 human epidermoid carcinoma cell line. Structural differences influenced the light-induced toxicity of the test compounds markedly. Compared to the initial tetraphenyl aza-BODIPY derivative, the compound bearing two hydrophilic triethylene glycol side chains showed substantial, more than 250-fold, photodynamic activity with no dark toxicity. Our newly synthesized aza-BODIPY derivative, acting in the nanomolar range, might serve as a promising candidate for the design of more active and selective photosensitizers. LA - English DB - MTMT ER - TY - JOUR AU - Csenki, Zsolt Imre AU - Bartók, Tibor AU - Bock, Illés AU - Horváth, Levente AU - Lemli, Beáta AU - Zsidó, Balázs Zoltán AU - Angeli, Cserne AU - Hetényi, Csaba AU - Szabó, István AU - Urbányi, Béla AU - Kovács, Melinda AU - Poór, Miklós TI - Interaction of Fumonisin B1, N-Palmitoyl-Fumonisin B1, 5-O-Palmitoyl-Fumonisin B1, and Fumonisin B4 Mycotoxins with Human Serum Albumin and Their Toxic Impacts on Zebrafish Embryos JF - BIOMOLECULES J2 - BIOMOLECULES VL - 13 PY - 2023 IS - 5 PG - 17 SN - 2218-273X DO - 10.3390/biom13050755 UR - https://m2.mtmt.hu/api/publication/33777591 ID - 33777591 N1 - Funding Agency and Grant Number: Hungarian National Research, Development and Innovation Office [FK138184]; Source of the National Research, Development and Innovation Fund; Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences [BO/00669/20/4]; Hungarian National Laboratory [RRF-2.3.1-21-2022-00007]; PTE AOK [KA-2022-26]; European Union; European Social Fund [EFOP-3.6.1-16-2016-00004]; Ministry of Innovation and Technology within the framework of the Thematic Excellence Programme 2021; National Defense and Security sub-programme [TKP2021-NVA-22] Funding text: The project is supported by the Hungarian National Research, Development and Innovation Office (FK138184) and by the UNKP-22-5 New National Excellence Program of the Ministry for Culture and Innovation from the Source of the National Research, Development and Innovation Fund (M.P.). This project was supported by the Janos Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00669/20/4; Z.C.). The support of the Hungarian National Laboratory project, RRF-2.3.1-21-2022-00007 is gratefully acknowledged. Molecular modeling studies of C.H. and B.Z.Z. were supported by the PTE AOK KA-2022-26 grant. The project has also been supported by the European Union and co-financed by the European Social Fund (Project name and code: Comprehensive Development for Implementing Smart Specialization Strategies at the University of Pecs, EFOP-3.6.1-16-2016-00004). This research was supported by the Ministry of Innovation and Technology within the framework of the Thematic Excellence Programme 2021, National Defense and Security sub-programme (TKP2021-NVA-22). LA - English DB - MTMT ER -