TY - JOUR AU - Kerekes, György AU - Bodoki, Levente AU - Hamar, Attila AU - Karancsiné Pusztai, Anita AU - Tajti, Gábor AU - Katkó, Mónika AU - Végh, Edit AU - Pethő, Zsófia AU - Bodnár, Nóra AU - Horváth, Ágnes AU - Soós, B. AU - Szamosi, Szilvia AU - Hascsi, Z. AU - Harangi, Mariann AU - Panyi, György AU - Szűcs, Gabriella AU - Szekanecz, Zoltán TI - AB0237 EFFECTS OF ONE-YEAR TOFACITINIB THERAPY ON ANGIOGENIC BIOMARKERS IN RHEUMATOID ARTHRITIS JF - ANNALS OF THE RHEUMATIC DISEASES J2 - ANN RHEUM DIS VL - 82 PY - 2023 IS - S1 SP - 1303 EP - 1303 PG - 1 SN - 0003-4967 DO - 10.1136/annrheumdis-2023-eular.2331 UR - https://m2.mtmt.hu/api/publication/34775337 ID - 34775337 LA - English DB - MTMT ER - TY - JOUR AU - Kerekes, György AU - Czókolyová, Monika AU - Hamar, Attila AU - Karancsiné Pusztai, Anita AU - Tajti, Gábor AU - Katkó, Mónika AU - Végh, Edit AU - Pethő, Zsófia AU - Bodnár, Nóra AU - Horváth, Ágnes AU - Soós, Boglárka AU - Szamosi, Szilvia AU - Hascsi, Zsolt AU - Harangi, Mariann AU - Hodosi, Katalin AU - Panyi, György AU - Seres, Tamás AU - Szűcs, Gabriella AU - Szekanecz, Zoltán TI - Effects of 1-year tofacitinib therapy on angiogenic biomarkers in rheumatoid arthritis JF - RHEUMATOLOGY (UNITED KINGDOM) J2 - RHEUMATOLOGY VL - 62 PY - 2023 IS - SI3 SP - SI304 EP - SI312 SN - 1462-0324 DO - 10.1093/rheumatology/kead502 UR - https://m2.mtmt.hu/api/publication/34215318 ID - 34215318 LA - English DB - MTMT ER - TY - JOUR AU - Fehér, Ádám AU - Pethő, Zoltán Dénes AU - Szántó, Gábor Tibor AU - Klekner, Álmos AU - Tajti, Gábor AU - Batta, Gyula Gábor (Ifj.) AU - Hortobágyi, Tibor AU - Varga, Zoltán AU - Schwab, Albrecht AU - Panyi, György TI - Mapping the functional expression of auxiliary subunits of KCa1.1 in glioblastoma JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 12 PY - 2022 IS - 1 PG - 14 SN - 2045-2322 DO - 10.1038/s41598-022-26196-w UR - https://m2.mtmt.hu/api/publication/33398474 ID - 33398474 AB - Glioblastoma (GBM) is the most aggressive glial tumor, where ion channels, including K Ca 1.1, are candidates for new therapeutic options. Since the auxiliary subunits linked to K Ca 1.1 in GBM are largely unknown we used electrophysiology combined with pharmacology and gene silencing to address the functional expression of K Ca 1.1/ β subunits complexes in both primary tumor cells and in the glioblastoma cell line U-87 MG. The pattern of the sensitivity (activation/inhibition) of the whole-cell currents to paxilline, lithocholic acid, arachidonic acid, and iberiotoxin; the presence of inactivation of the whole-cell current along with the loss of the outward rectification upon exposure to the reducing agent DTT collectively argue that K Ca 1.1/β3 complex is expressed in U-87 MG. Similar results were found using human primary glioblastoma cells isolated from patient samples. Silencing the β3 subunit expression inhibited carbachol-induced Ca 2+ transients in U-87 MG thereby indicating the role of the K Ca 1.1/β3 in the Ca 2+ signaling of glioblastoma cells. Functional expression of the K Ca 1.1/β3 complex, on the other hand, lacks cell cycle dependence. We suggest that the K Ca 1.1/β3 complex may have diagnostic and therapeutic potential in glioblastoma in the future. LA - English DB - MTMT ER - TY - JOUR AU - Czókolyová, Monika AU - Hamar, Attila AU - Karancsiné Pusztai, Anita AU - Tajti, Gábor AU - Végh, Edit AU - Pethő, Zsófia AU - Bodnár, Nóra AU - Horváth, Ágnes AU - Boglárka, Soós AU - Szamosi, Szilvia AU - Szentpéteri, Anita AU - Seres, Ildikó AU - Harangi, Mariann AU - Paragh, György AU - Kerekes, György AU - Bodoki, Levente AU - Katalin, Hodosi AU - Tamás, Seres AU - Panyi, György AU - Szekanecz, Zoltán AU - Szűcs, Gabriella TI - Effects of One-Year Tofacitinib Therapy on Lipids and Adipokines in Association with Vascular Pathophysiology in Rheumatoid Arthritis JF - BIOMOLECULES J2 - BIOMOLECULES VL - 12 PY - 2022 IS - 10 SN - 2218-273X DO - 10.3390/biom12101483 UR - https://m2.mtmt.hu/api/publication/33153228 ID - 33153228 AB - Background: Cardiovascular (CV) morbidity, mortality and metabolic syndrome are associated with rheumatoid arthritis (RA). A recent trial has suggested increased risk of major CV events (MACE) upon the Janus kinase (JAK) inhibitor tofacitinib compared with anti-tumor necrosis factor α (TNF-α) therapy. In our study, we evaluated lipids and other metabolic markers in relation to vascular function and clinical markers in RA patients undergoing one-year tofacitinib therapy. Patients and methods: Thirty RA patients treated with either 5 mg or 10 mg bid tofacitinib were included in a 12-month follow-up study. Various lipids, paraoxonase (PON1), myeloperoxidase (MPO), thrombospondin-1 (TSP-1) and adipokine levels, such as adiponectin, leptin, resistin, adipsin and chemerin were determined. In order to assess flow-mediated vasodilation (FMD), common carotid intima-media thickness (IMT) and arterial pulse-wave velocity (PWV) ultrasonography were performed. Assessments were carried out at baseline, and 6 and 12 months after initiating treatment. Results: One-year tofacitinib therapy significantly increased TC, HDL, LDL, APOA, APOB, leptin, adipsin and TSP-1, while significantly decreasing Lp(a), chemerin, PON1 and MPO levels. TG, lipid indices (TC/HDL and LDL/HDL), adiponectin and resistin showed no significant changes. Numerous associations were found between lipids, adipokines, clinical markers and IMT, FMD and PWV (p < 0.05). Regression analysis suggested, among others, association of BMI with CRP and PWV (p < 0.05). Adipokines variably correlated with age, BMI, CRP, CCP, FMD, IMT and PWV, while MPO, PON1 and TSP-1 variably correlated with age, disease duration, BMI, RF and PWV (p < 0.05). Conclusions: JAK inhibition by tofacitinib exerts balanced effects on lipids and other metabolic markers in RA. Various correlations may exist between metabolic, clinical parameters and vascular pathophysiology during tofacitinib treatment. Complex assessment of lipids, metabolic factors together with clinical parameters and vascular pathophysiology may be utilized in clinical practice to determine and monitor the CV status of patients in relation with clinical response to JAK inhibition. LA - English DB - MTMT ER - TY - JOUR AU - Csóti, Ágota AU - del Carmen Nájera Meza, Rosby AU - Bogár, Ferenc AU - Tajti, Gábor AU - Szántó, Gábor Tibor AU - Varga, Zoltán AU - Gurrola, Georgina B. AU - Tóth, Gábor AU - Possani, Lourival D. AU - Panyi, György TI - sVmKTx, a transcriptome analysis-based synthetic peptide analogue of Vm24, inhibits Kv1.3 channels of human T cells with improved selectivity JF - BIOCHEMICAL PHARMACOLOGY J2 - BIOCHEMIC PHARMACOL VL - 199 PY - 2022 PG - 14 SN - 0006-2952 DO - 10.1016/j.bcp.2022.115023 UR - https://m2.mtmt.hu/api/publication/32803926 ID - 32803926 LA - English DB - MTMT ER - TY - JOUR AU - Naseem, Muhammad Umair AU - Tajti, Gábor AU - Gáspár, Attila AU - Szántó, Gábor Tibor AU - Borrego Terrazas, Jesus Angel AU - Panyi, György TI - Optimization of Pichia pastoris Expression System for High-Level Production of Margatoxin JF - FRONTIERS IN PHARMACOLOGY J2 - FRONT PHARMACOL VL - 12 PY - 2021 PG - 18 SN - 1663-9812 DO - 10.3389/fphar.2021.733610 UR - https://m2.mtmt.hu/api/publication/32476083 ID - 32476083 N1 - Funding Agency and Grant Number: Tempus Public Foundation; [OTKA K119417]; [EFOP-3.6.1-16-2016-00022]; [GINOP2.3.2-15-2016-00044] Funding text: The following grants supported the work: OTKA K119417 (GP), EFOP-3.6.1-16-2016-00022 (MUN, JB, and GP), and GINOP2.3.2-15-2016-00044 (GP). This work was supported by the Stipendium Hungaricum Scholarship by the Tempus Public Foundation (to MUN). AB - Margatoxin (MgTx) is a high-affinity blocker of voltage-gated potassium (Kv) channels. It inhibits Kv1.1-Kv1.3 ion channels in picomolar concentrations. This toxin is widely used to study physiological function of Kv ion channels in various cell types, including immune cells. Isolation of native MgTx in large quantities from scorpion venom is not affordable. Chemical synthesis and recombinant production in Escherichia coli need in vitro oxidative refolding for proper disulfide bond formation, resulting in a very low yield of peptide production. The Pichia pastoris expression system offers an economical approach to overcome all these limitations and gives a higher yield of correctly refolded recombinant peptides. In this study, improved heterologous expression of recombinant MgTx (rMgTx) in P. pastoris was obtained by using preferential codons, selecting the hyper-resistant clone against Zeocin, and optimizing the culturing conditions. About 36 +/- 4 mg/L of >98% pure His-tagged rMgTx (TrMgTx) was produced, which is a threefold higher yield than has been previously reported. Proteolytic digestion of TrMgTx with factor Xa generated untagged rMgTx (UrMgTx). Both TrMgTx and UrMgTx blocked the Kv1.2 and Kv1.3 currents (patch-clamp) (K ( d ) for Kv1.2 were 64 and 14 pM, and for Kv1.3, 86 and 50 pM, respectively) with comparable potency to the native MgTx. The analysis of the binding kinetics showed that TrMgTx had a lower association rate than UrMgTx for both Kv1.2 and Kv1.3. The dissociation rate of both the analogues was the same for Kv1.3. However, in the case of Kv1.2, TrMgTx showed a much higher dissociation rate with full recovery of the block than UrMgTx. Moreover, in a biological functional assay, both peptides significantly downregulated the expression of early activation markers IL2R and CD40L in activated CD4(+) T-EM lymphocytes whose activation was Kv1.3 dependent. In conclusion, the authors report that the Pichia expression system is a powerful method to produce disulfide-rich peptides, the overexpression of which could be enhanced noticeably through optimization strategies, making it more cost-effective. Since the presence of the His-tag on rMgTx only mildly altered the block equilibrium and binding kinetics, recombinant toxins could be used in ion channel research without removing the tag and could thus reduce the cost and time demand for toxin production. LA - English DB - MTMT ER - TY - JOUR AU - Hamar, Attila AU - Szekanecz, Zoltán AU - Karancsiné Pusztai, Anita AU - Czókolyová, Monika AU - Végh, E. AU - Pethő, Zoltán Dénes AU - Bodnár, Nóra AU - Gulyás, Katalin AU - Horváth, Á. AU - Soós, B. AU - Bodoki, Levente AU - Bhattoa Harjit, Pál AU - Nagy, Gábor AU - Tajti, Gábor AU - Panyi, György AU - Szekanecz, Éva AU - Domján, A. AU - Hodosi, K. AU - Szántó, Sándor Zoltán AU - Szűcs, Gabriella AU - Szamosi, Szilvia TI - Effects of one-year tofacitinib therapy on bone metabolism in rheumatoid arthritis JF - OSTEOPOROSIS INTERNATIONAL J2 - OSTEOPOROSIS INT VL - 32 PY - 2021 IS - 8 SP - 1621 EP - 1629 PG - 9 SN - 0937-941X DO - 10.1007/s00198-021-05871-0 UR - https://m2.mtmt.hu/api/publication/31878487 ID - 31878487 N1 - 302246 LA - English DB - MTMT ER - TY - JOUR AU - Varga, Zoltán AU - Tajti, Gábor AU - Panyi, György TI - The Kv1.3 K+ channel in the immune system and its “precision pharmacology” using peptide toxins JF - BIOLOGIA FUTURA J2 - BIOL FUTURA VL - 72 PY - 2021 IS - 1 SP - 75 EP - 83 PG - 9 SN - 2676-8615 DO - 10.1007/s42977-021-00071-7 UR - https://m2.mtmt.hu/api/publication/31868210 ID - 31868210 N1 - Funding Agency and Grant Number: University of Debrecen; European UnionEuropean Commission; European Regional Development FundEuropean Commission; OTKAOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [K119417, EFOP-3.6.216-2017-00006]; [GINOP-2.3.2-15-2016-00015] Funding text: Open Access funding provided by University of Debrecen. The publication is supported by the GINOP-2.3.2-15-2016-00015 project (G.T. and G.P). The project is co-financed by the European Union and the European Regional Development Fund. The authors acknowledge the support of OTKA K119417 (G.P.) and EFOP-3.6.216-2017-00006 (G.P.). LA - English DB - MTMT ER - TY - JOUR AU - Tajti, Gábor AU - Szántó, Gábor Tibor AU - Csóti, Ágota AU - Racz, G. AU - Evaristo, C. AU - Hajdu, Péter Béla AU - Panyi, György TI - Immunomagnetic separation is a suitable method for electrophysiology and ion channel pharmacology studies on T cells JF - CHANNELS J2 - CHANNELS VL - 15 PY - 2021 IS - 1 SP - 53 EP - 66 PG - 14 SN - 1933-6950 DO - 10.1080/19336950.2020.1859753 UR - https://m2.mtmt.hu/api/publication/31813030 ID - 31813030 N1 - Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary RD Reagents Chemical Biology, Miltenyi Biotec B.V. Co. KG, Bergisch Gladbach, Germany Department of Biophysics and Cell Biology, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary Export Date: 15 January 2021 Correspondence Address: Panyi, G.; Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, 1 Egyetem Ter, Life Science Bldg. 2.305, Hungary; email: panyi@med.unideb.hu AB - Ion channels play pivotal role in the physiological and pathological function of immune cells. As immune cells represent a functionally diverse population, subtype-specific functional studies, such as single-cell electrophysiology require proper subset identification and separation. Magnetic-activated cell sorting (MACS) techniques provide an alternative to fluorescence-activated cell sorting (FACS), however, the potential impact of MACS-related beads on the biophysical and pharmacological properties of the ion channels were not studied yet. We studied the aforementioned properties of the voltage-gated Kv1.3 K+ channel in activated CD4+ T-cells as well as the membrane capacitance using whole-cell patch-clamp following immunomagnetic positive separation, using the REAlease® kit. This kit allows three experimental configurations: bead-bound configuration, bead-free configuration following the removal of magnetic beads, and the label-free configuration following removal of CD4 recognizing antibody fragments. As controls, we used FACS separation as well as immunomagnetic negative selection. The membrane capacitance and of the biophysical parameters of Kv1.3 gating, voltage-dependence of steady-state activation and inactivation kinetics of the current were not affected by the presence of MACS-related compounds on the cell surface. We found subtle differences in the activation kinetics of the Kv1.3 current that could not be explained by the presence of MACS-related compounds. Neither the equilibrium block of Kv1.3 by TEA+ or charybdotoxin (ChTx) nor the kinetics of ChTx block are affected by the presence of the magnetics beads on the cell surface. Based on our results MACS is a suitable method to separate cells for studying ion channels in non-excitable cells, such as T-lymphocytes. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. LA - English DB - MTMT ER - TY - CHAP AU - Mészáros, Beáta AU - Csóti, Ágota AU - Vörös, Orsolya AU - Tajti, Gábor AU - Panyi, György ED - Rakonczay, Zoltán ED - Kiss, Lóránd TI - Ion channel gene transcripts in chorion-derived mesenchymal stem cells T2 - Proceedings of the EFOP-3.6.2-16-2017-00006 (LIVE LONGER) project PB - University of Szeged CY - Szeged SN - 9789633067642 PY - 2020 UR - https://m2.mtmt.hu/api/publication/31672869 ID - 31672869 AB - Introduction: Mesenchymal stem cells (MSCs) have gained interest for regenerative medicine. Several studies suggested the attractive therapeutic potential of the placenta-derived MSC, however, literature is insufficient regarding the expression of ion channels in chorion/placenta-derived MSCs (cMSCs). Since ion channels are known to regulate many cell functions in non-excitable cells as well, our aim was to study the expression of ion channels in cMSCs. Methods: The heterogeneity of cMSC culture is a challenge when studying ion channels. We designed a cell sorting system using multicolor flow cytometry which can distinguish MSCs from other cell types within cMSCs culture. We analysed the mRNA expression of different cell type markers and ion channels using qPCR. Results: mRNA markers of fibroblast, syncytiotrophoblasts, smooth muscle and endothelial cells were detected in cMSCs. We designed a cell sorting system using the combination of fluorophore-conjugated anti-CD73, -CD90, -CD34, - CD45 antibodies. Sorted cMSCs also expressed GATA, Nanog, Oct4, Sox2 stem cell markers. We detected the mRNA of Kv1.3, Kv4.2, Kv4.3, and Kv10.1, KCa1.1 associated with β1-, β2a-, β3b, c, d-subunits, Nav1.2, Nav1.7, CLCN2-4 and CLCN6-7 channels in sorted and non-sorted cMSCs. Conclusions: Multiple ion channel mRNAs were detected in cMSCs. The mRNA phenotypes of sorted and non-sorted cMSCs, were similar, however, this finding does not exclude qualitative and quantitative differences in the expression at protein level. Cell sorting is recommended for single cell electrophysiology methods aimed at identifying the functional expression of the channels. Acknowledgements: This work was supported by EFOP 3.6.2-16-2017-00006 (LIVE LONGER). LA - English DB - MTMT ER -