TY - JOUR AU - Héja, László AU - Simon, Ágnes AU - Kardos, Julianna TI - Simulation of gap junction formation reveals critical role of Cys disulfide redox state in connexin hemichannel docking JF - CELL COMMUNICATION AND SIGNALING J2 - CELL COMM SIGN VL - 22 PY - 2024 IS - 1 SN - 1478-811X DO - 10.1186/s12964-023-01439-z UR - https://m2.mtmt.hu/api/publication/34768350 ID - 34768350 LA - English DB - MTMT ER - TY - JOUR AU - Héja, László AU - Kardos, Julianna TI - GABA fluctuations driven by astrocytic Glu-GABA exchange explain synaptic acuity JF - Cell Signaling J2 - Cell Signal VL - 1 PY - 2023 IS - 1 SP - 76 EP - 80 PG - 5 SN - 2837-8253 DO - 10.46439/signaling.1.016 UR - https://m2.mtmt.hu/api/publication/34718118 ID - 34718118 LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Zsolt AU - Skatchkov, Serguei N. AU - Szabó, Zsolt AU - Qahtan, Saif AU - Méndez-González, Miguel P. AU - Malpica-Nieves, Christian J. AU - Eaton, Misty J. AU - Kardos, Julianna AU - Héja, László TI - Putrescine Intensifies Glu/GABA Exchange Mechanism and Promotes Early Termination of Seizures JF - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES J2 - INT J MOL SCI VL - 23 PY - 2022 IS - 15 SN - 1661-6596 DO - 10.3390/ijms23158191 UR - https://m2.mtmt.hu/api/publication/33031938 ID - 33031938 N1 - Department of Biology, Savaria University Centre, ELTE Eötvös Loránd University, Károlyi Gáspár tér 4, Szombathely, 9700, Hungary Department of Physiology, Universidad Central del Caribe, Bayamon, 00960, Puerto Rico Department of Biochemistry, Universidad Central del Caribe, Bayamon, 00960, Puerto Rico Functional Pharmacology Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, Budapest, 1117, Hungary School of Chemistry, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/A, Budapest, 1117, Hungary College of Science, University of Al-Qadisiyah, Al-Diwaniyah, 58001, Iraq Natural Sciences Department, University of Puerto Rico in Aguadilla, Aguadilla, 00604, Puerto Rico Department of Science and Technology, Antilles Adventist University, Mayagüez, 00681, Puerto Rico Export Date: 25 October 2022 Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Magyar Tudósok Körútja 2, Hungary; email: heja.laszlo@ttk.hu LA - English DB - MTMT ER - TY - JOUR AU - Héja, László AU - Simon, Ágnes AU - Szabó, Zsolt AU - Kardos, Julianna TI - Connexons coupling to gap junction channel: Potential role for extracellular protein stabilization centers JF - BIOMOLECULES J2 - BIOMOLECULES VL - 12 PY - 2022 IS - 1 SN - 2218-273X DO - 10.3390/biom12010049 UR - https://m2.mtmt.hu/api/publication/32612048 ID - 32612048 N1 - Export Date: 24 January 2022 Correspondence Address: Héja, L.; Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, Hungary; email: heja.laszlo@ttk.hu Chemicals/CAS: cystine, 24645-67-8, 56-89-3, 6020-39-9 Funding details: National Research, Development and Innovation Office, OTKA K124558 Funding text 1: Funding: This work was supported by National Research, Development and Innovation Office grant OTKA K124558. AB - Connexin (Cx) proteins establish intercellular gap junction channels (Cx GJCs) through coupling of two apposed hexameric Cx hemichannels (Cx HCs, connexons). Pre-and post-GJ interfaces consist of extracellular EL1 and EL2 loops, each with three conserved cysteines. Previously, we reported that known peptide inhibitors, mimicking a variety of Cx43 sequences, appear non-selective when binding to homomeric Cx43 vs. Cx36 GJC homology model subtypes. In pursuit of finding potentially Cx subtype-specific inhibitors of connexon-connexon coupling, we aimed at to understand better how the GJ interface is formed. Here we report on the discovery of Cx GJC subtype-specific protein stabilization centers (SCs) featuring GJ interface architecture. First, the Cx43 GJC homology model, embedded in two opposed membrane bilayers, has been devised. Next, we endorsed the fluctuation dynamics of SCs of the interface domain of Cx43 GJC by applying standard molecular dynamics under open and closed cystine disulfide bond (CS-SC) preconditions. The simulations confirmed the major role of of the unique trans-GJ SC pattern comprising conserved (55N, 56T) and non-conserved (57Q) residues of the apposed EL1 loops in the stabilization of the GJC complex. Importantly, clusters of SC patterns residing close to the GJ interface domain appear to orient the interface formation via the numerous SCs between EL1 and EL2. These include central54CS-S198C or61CS-S192C contacts with residues 53R, 54C, 55N, 197D, 199F or 64V, 191P, respectively. In addition, we revealed that GJC interface formation is favoured when the psi dihedral angle of the nearby 193P residue is stable around 180◦ and the interface SCs disappear when this angle moves to the 0◦ to −45◦ range. The potential of the association of non-conserved residues with SC motifs in connexon-connexon coupling makes the development of Cx subtype-specific inhibitors viable. © 2021 by the authors. Licensee MDPI, Basel, Switzerland. LA - English DB - MTMT ER - TY - JOUR AU - Kovács, Zsolt AU - Skatchkov, Serguei N. AU - Veh, Rüdiger W. AU - Szabó, Zsolt AU - Németh, Krisztina AU - Szabó, Pál Tamás AU - Kardos, Julianna AU - Héja, László TI - Critical Role of Astrocytic Polyamine and GABA Metabolism in Epileptogenesis JF - FRONTIERS IN CELLULAR NEUROSCIENCE J2 - FRONT CELL NEUROSCI VL - 15 PY - 2022 PG - 15 SN - 1662-5102 DO - 10.3389/fncel.2021.787319 UR - https://m2.mtmt.hu/api/publication/32578354 ID - 32578354 N1 - Department of Biology, ELTE Eötvös Loránd University, Savaria University Centre, Szombathely, Hungary Department of Physiology, Universidad Central Del Caribe, Bayamon, PR, United States Department of Biochemistry, Universidad Central Del Caribe, Bayamon, PR, United States Institut für Zell- und Neurobiologie, Centrum 2, Charité - Universitätsmedizin Berlin, Berlin, Germany Functional Pharmacology Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Budapest, Hungary MS Metabolomics Research Group, Centre for Structural Study, Research Centre for Natural Sciences, Eötvös Loránd Research Network, Budapest, Hungary Export Date: 28 February 2022 Correspondence Address: Skatchkov, S.N.; Department of Physiology, United States; email: serguei.skatchkov@uccaribe.edu Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Hungary; email: heja.laszlo@ttk.hu Chemicals/CAS: 4 (2 hydroxyethyl) 1 piperazineethanesulfonic acid, 7365-45-9; 4 aminobutyric acid, 28805-76-7, 56-12-2; acetonitrile, 75-05-8; alcohol, 64-17-5; alpha amino 3 hydroxy 5 methyl 4 isoxazolepropionic acid, 77521-29-0; ammonium sulfate, 7783-20-2; arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; bicarbonate, 144-55-8, 71-52-3; calcium chloride, 10043-52-4; carbon dioxide, 124-38-9, 58561-67-4; diaminobenzidine, 7411-49-6, 91-95-2; dimethyl sulfoxide, 67-68-5; eflornithine, 67037-37-0, 70052-12-9; ethanolamine, 141-43-5; formic acid, 64-18-6, 71-47-6; gluconic acid, 133-42-6, 526-95-4, 66664-08-2; glucose, 50-99-7, 84778-64-3; glutaraldehyde, 111-30-8, 37245-61-7; histamine, 51-45-6, 56-92-8, 93443-21-1; hydrogen peroxide, 7722-84-1; imidazole, 1467-16-9, 288-32-4; immunoglobulin G, 97794-27-9; isoflurane, 26675-46-7; levetiracetam, 102767-28-2; lidocaine, 137-58-6, 24847-67-4, 56934-02-2, 73-78-9; lysine, 56-87-1, 6899-06-5, 70-54-2; magnesium sulfate, 7487-88-9; methyl green, 54327-10-5; n methyl dextro aspartic acid, 6384-92-5; nitrogen, 7727-37-9; ornithine, 70-26-8, 7006-33-9; ornithine decarboxylase, 9024-60-6; paraformaldehyde, 30525-89-4; peroxidase, 9003-99-0; picric acid, 14798-26-6, 88-89-1; potassium chloride, 7447-40-7; putrescine, 110-60-1, 333-93-7; sodium borohydride, 16940-66-2; sodium chloride, 7647-14-5, 23724-87-0, 49658-21-1; sodium dihydrogen phosphate, 7558-80-7, 7632-05-5; spermidine, 124-20-9, 334-50-9; sucrose, 122880-25-5, 57-50-1; water, 7732-18-5 Tradenames: 1100, Agilent, United States; Bioamp4; BX51WI, Olympus, Japan; DP30BW, Olympus, Japan; MX7500; QTRAP 6500, Sciex, United States; VT1000S, Leica, Germany Manufacturers: Vector, Germany; Tocris, United Kingdom; Egis, Hungary; TCI, Japan; Ivoclar, Liechtenstein; Sigma Aldrich, United StatesLeica, Germany; Olympus, Japan; Agilent, United States; Axon, United States; Sciex, United States; Sutter, United States; World Precision Instruments, United States Funding details: National Institutes of Health, NIH, NIMHD-PRCTRC-8U54MD007587-03 Funding details: National Institute of General Medical Sciences, NIGMS, G12MD007583 Funding details: National Institute of Neurological Disorders and Stroke, NINDS, R15-NS-116478, RO1-NS-065201 Funding details: Magyar Tudományos Akadémia, MTA Funding details: National Research, Development and Innovation Office, OTKA K124558 Funding text 1: This work was supported by the National Research, Development and Innovation Office grant OTKA K124558 and by the National Institutes of Health grants: NIH NINDS RO1-NS-065201 (to SS), NIH NINDS R15-NS-116478 (to SS), and NIH NIMHD-PRCTRC-8U54MD007587-03 (to UCC and PMS consortium); NIH NIGMS G12MD007583 (UCC Core facilities). LH is a recipient of the János Bolyai Scholarship of the Hungarian Academy of Sciences. Funding text 2: This work was supported by the National Research, Development and Innovation Office grant OTKA K124558 and by the National Institutes of Health grants: NIH NINDS RO1-NS-065201 (to SS), NIH NINDS R15-NS-116478 (to SS), and NIH NIMHD-PRCTRC-8U54MD007587-03 (to UCC and PMS consortium); NIH NIGMS G12MD007583 (UCC Core facilities). LH is a recipient of the J?nos Bolyai Scholarship of the Hungarian Academy of Sciences. LA - English DB - MTMT ER - TY - JOUR AU - Szabó, Zsolt AU - Péter, Márton AU - Héja, László AU - Kardos, Julianna TI - Dual Role for Astroglial Copper-Assisted Polyamine Metabolism during Intense Network Activity JF - BIOMOLECULES J2 - BIOMOLECULES VL - 11 PY - 2021 IS - 4 SN - 2218-273X DO - 10.3390/biom11040604 UR - https://m2.mtmt.hu/api/publication/31971626 ID - 31971626 N1 - Functional Pharmacology Research Group, Research Centre for Natural Sciences, Institute of Organic Chemistry, Budapest, H-1117, Hungary Hevesy György Ph.D. School of Chemistry, ELTE Eötvös Loránd University, Budapest, H-1117, Hungary Export Date: 28 July 2021 Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Hungary; email: heja.laszlo@ttk.hu Funding details: Hungarian Scientific Research Fund, OTKA, K124558 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: Funding: This research was partly supported by the grant OTKA K124558. László Héja is a recipient of the János Bolyai Scholarship of the Hungarian Academy of Sciences. Funding text 2: This research was partly supported by the grant OTKA K124558. L?szl? H?ja is a recipient of the J?nos Bolyai Scholarship of the Hungarian Academy of Sciences. Functional Pharmacology Research Group, Research Centre for Natural Sciences, Institute of Organic Chemistry, Budapest, H-1117, Hungary Hevesy György Ph.D. School of Chemistry, ELTE Eötvös Loránd University, Budapest, H-1117, Hungary Export Date: 29 July 2021 Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Hungary; email: heja.laszlo@ttk.hu Funding details: Hungarian Scientific Research Fund, OTKA, K124558 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: Funding: This research was partly supported by the grant OTKA K124558. László Héja is a recipient of the János Bolyai Scholarship of the Hungarian Academy of Sciences. Funding text 2: This research was partly supported by the grant OTKA K124558. L?szl? H?ja is a recipient of the J?nos Bolyai Scholarship of the Hungarian Academy of Sciences. Functional Pharmacology Research Group, Research Centre for Natural Sciences, Institute of Organic Chemistry, Budapest, H-1117, Hungary Hevesy György Ph.D. School of Chemistry, ELTE Eötvös Loránd University, Budapest, H-1117, Hungary Export Date: 23 September 2021 Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Hungary; email: heja.laszlo@ttk.hu Chemicals/CAS: calcium ion, 14127-61-8; copper, 15158-11-9, 7440-50-8; glutamine, 56-85-9, 6899-04-3; silver nitrate, 7761-88-8 Funding details: Hungarian Scientific Research Fund, OTKA, K124558 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: Funding: This research was partly supported by the grant OTKA K124558. László Héja is a recipient of the János Bolyai Scholarship of the Hungarian Academy of Sciences. Funding text 2: This research was partly supported by the grant OTKA K124558. L?szl? H?ja is a recipient of the J?nos Bolyai Scholarship of the Hungarian Academy of Sciences. Functional Pharmacology Research Group, Research Centre for Natural Sciences, Institute of Organic Chemistry, Budapest, H-1117, Hungary Hevesy György Ph.D. School of Chemistry, ELTE Eötvös Loránd University, Budapest, H-1117, Hungary Export Date: 24 September 2021 Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Hungary; email: heja.laszlo@ttk.hu Chemicals/CAS: calcium ion, 14127-61-8; copper, 15158-11-9, 7440-50-8; glutamine, 56-85-9, 6899-04-3; silver nitrate, 7761-88-8 Funding details: Hungarian Scientific Research Fund, OTKA, K124558 Funding details: Magyar Tudományos Akadémia, MTA Funding text 1: Funding: This research was partly supported by the grant OTKA K124558. László Héja is a recipient of the János Bolyai Scholarship of the Hungarian Academy of Sciences. Funding text 2: This research was partly supported by the grant OTKA K124558. L?szl? H?ja is a recipient of the J?nos Bolyai Scholarship of the Hungarian Academy of Sciences. LA - English DB - MTMT ER - TY - JOUR AU - Héja, László AU - Szabó, Zsolt AU - Péter, Márton AU - Kardos, Julianna TI - Spontaneous Ca2+ Fluctuations Arise in Thin Astrocytic Processes With Real 3D Geometry JF - FRONTIERS IN CELLULAR NEUROSCIENCE J2 - FRONT CELL NEUROSCI VL - 15 PY - 2021 SN - 1662-5102 DO - 10.3389/fncel.2021.617989 UR - https://m2.mtmt.hu/api/publication/31925857 ID - 31925857 N1 - Funding Agency and Grant Number: National Research, Development, and Innovation Office [OTKA K124558]; Hungarian Academy of SciencesHungarian Academy of Sciences Funding text: This work was supported by National Research, Development, and Innovation Office grant OTKA K124558. LH is a recipient of the Janos Bolyai Scholarship of the Hungarian Academy of Sciences. Functional Pharmacology Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences (MTA), Budapest, Hungary Hevesy György PhD School of Chemistry, ELTE Eötvös Loránd University, Budapest, Hungary Cited By :1 Export Date: 29 July 2021 Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Hungary; email: heja.laszlo@ttk.mta.hu Funding details: Magyar Tudományos Akadémia, MTA Funding details: National Research, Development and Innovation Office, OTKA K124558 Funding text 1: We thank P?ter Somogyi FRS, FMedSci, Professor of Neurobiology, Department of Pharmacology, University of Oxford for valuable discussions. Funding. This work was supported by National Research, Development, and Innovation Office grant OTKA K124558. LH is a recipient of the J?nos Bolyai Scholarship of the Hungarian Academy of Sciences. Functional Pharmacology Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of Sciences (MTA), Budapest, Hungary Hevesy György PhD School of Chemistry, ELTE Eötvös Loránd University, Budapest, Hungary Cited By :2 Export Date: 23 September 2021 Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Hungary; email: heja.laszlo@ttk.mta.hu Chemicals/CAS: calcium, 7440-70-2, 14092-94-5; calcium ion, 14127-61-8; sodium ion, 17341-25-2 Funding details: Magyar Tudományos Akadémia, MTA Funding details: National Research, Development and Innovation Office, OTKA K124558 Funding text 1: We thank P?ter Somogyi FRS, FMedSci, Professor of Neurobiology, Department of Pharmacology, University of Oxford for valuable discussions. Funding. This work was supported by National Research, Development, and Innovation Office grant OTKA K124558. LH is a recipient of the J?nos Bolyai Scholarship of the Hungarian Academy of Sciences. LA - English DB - MTMT ER - TY - JOUR AU - Simon, Ágnes AU - Magyar, Csaba AU - Héja, László AU - Kardos, Julianna TI - Peptide Binding Sites of Connexin Proteins JF - CHEMISTRY J2 - CHEMISTRY VL - 2 PY - 2020 IS - 3 SP - 662 EP - 673 PG - 12 SN - 2624-8549 DO - 10.3390/chemistry2030042 UR - https://m2.mtmt.hu/api/publication/31795296 ID - 31795296 LA - English DB - MTMT ER - TY - JOUR AU - Héja, László AU - Kardos, Julianna TI - NCX activity generates spontaneous Ca2+ oscillations in the astrocytic leaflet microdomain JF - CELL CALCIUM J2 - CELL CALCIUM VL - 86 PY - 2020 IS - March 2020 SN - 0143-4160 DO - 10.1016/j.ceca.2019.102137 UR - https://m2.mtmt.hu/api/publication/31123982 ID - 31123982 N1 - Export Date: 13 January 2020 CODEN: CECAD Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Institute of Organic Chemistry, Research Centre for Natural Sciences, Hungarian Academy of SciencesHungary; email: heja.laszlo@ttk.mta.hu Chemicals/CAS: calcium ion, 14127-61-8; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; sodium ion, 17341-25-2 Funding details: K124558 . Funding text 1: This work was supported by grants VEKOP - 2.1.1-15-2016-00156 and National Research, Development and Innovation Office grant OTKA K124558 . Export Date: 23 February 2021 CODEN: CECAD Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Hungary; email: heja.laszlo@ttk.mta.hu Funding Agency and Grant Number: National Research, Development and Innovation Office [OTKA K124558]; [VEKOP-2.1.1-15-2016-00156] Funding text: This work was supported by grants VEKOP-2.1.1-15-2016-00156 and National Research, Development and Innovation Office grant OTKA K124558. Cited By :2 Export Date: 6 April 2021 CODEN: CECAD Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Hungary; email: heja.laszlo@ttk.mta.hu Cited By :2 Export Date: 7 April 2021 CODEN: CECAD Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Hungary; email: heja.laszlo@ttk.mta.hu Cited By :4 Export Date: 23 September 2021 CODEN: CECAD Correspondence Address: Héja, L.; Functional Pharmacology Research Group, Hungary; email: heja.laszlo@ttk.mta.hu Chemicals/CAS: calcium ion, 14127-61-8; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; sodium ion, 17341-25-2; calcium, 7440-70-2, 14092-94-5; Calcium; Sodium-Calcium Exchanger Funding details: OTKA K124558 Funding text 1: This work was supported by grants VEKOP-2.1.1-15-2016-00156 and National Research, Development and Innovation Office grant OTKA K124558. AB - The synergy between synaptic Glu release and astrocytic Glu-Na+ symport is essential to the signalling function of the tripartite synapse. Here we used kinetic data of astrocytic Glu transporters (EAAT) and the Na+/Ca2+ exchanger (NCX) to simulate Glu release, Glu uptake and subsequent Na+ and Ca2+ dynamics in the astrocytic leaflet microdomain following single release event. Model simulations show that Glu-Na+ symport differently affect intracellular [Na+] in synapses with different extent of astrocytic coverage. Surprisingly, NCX activity alone has been shown to generate markedly stable, spontaneous Ca2+ oscillation in the astrocytic leaflet. These on-going oscillations appear when NCX operates either in the forward or reverse direction. We conjecture that intrinsic NCX activity may play a prominent role in the generation of astrocytic Ca2+ oscillations. © 2019 The Authors LA - English DB - MTMT ER - TY - JOUR AU - Vincze, R. AU - Péter, Márton AU - Szabó, Zsolt AU - Kardos, Julianna AU - Kovács, Zsolt AU - Héja, László TI - Astrocytic gap junctions differentially affect seizures in absence and temporal lobe epilepsy models JF - GLIA J2 - GLIA VL - 67 PY - 2019 SP - E710 EP - E711 PG - 2 SN - 0894-1491 UR - https://m2.mtmt.hu/api/publication/31096625 ID - 31096625 N1 - Poszter Funding Agency and Grant Number: National Research, Development and Innovation Office grant [OTKA K124558]; [VEKOP-2.1.1-15-2016-00156] Funding text: This work was supported by grants VEKOP-2.1.1-15-2016-00156 and National Research, Development and Innovation Office grant OTKA K124558. Supplement: S1 LA - English DB - MTMT ER -