TY - CONF AU - Kokas, Márton AU - Kirchlechner-Farkas, Judit Mária AU - Gáspár, Dániel AU - Komlódi, Tímea AU - Ozohanics, Olivér AU - Környei, Zsuzsanna AU - Sváb, Gergely AU - Tretter, László TI - METABOLIKUS POLIHISZTOR VAGY EGYSZERŰ GLUTAMINGYÁR? – CITRÁTKÖR AZ ASZTROCITÁKBAN T2 - Membrán-Transzport konferencia : programfüzet PB - Pécsi Tudományegytem C1 - Sümeg C1 - Pécs PY - 2023 UR - https://m2.mtmt.hu/api/publication/34030843 ID - 34030843 LA - Hungarian DB - MTMT ER - TY - THES AU - Sváb, Gergely TI - Neuroprotektív vegyületek hatásmechanizmusának vizsgálata: a metilénkék és a vinpocetin mitokondriális célpontjai PY - 2023 DO - 10.14753/SE.2023.2792 UR - https://m2.mtmt.hu/api/publication/34509339 ID - 34509339 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Horváth, Gergő AU - Sváb, Gergely AU - Komlódi, Tímea AU - Ravasz, Dóra AU - Kacsó, Gergely AU - Dóczi, Judit AU - Chinopoulos, Christos AU - Ambrus, Attila AU - Tretter, László TI - Reverse and Forward Electron Flow-Induced H2O2 Formation Is Decreased in α-Ketoglutarate Dehydrogenase (α-KGDH) Subunit (E2 or E3) Heterozygote Knock Out Animals JF - ANTIOXIDANTS J2 - ANTIOXIDANTS-BASEL VL - 11 PY - 2022 IS - 8 PG - 19 SN - 2076-3921 DO - 10.3390/antiox11081487 UR - https://m2.mtmt.hu/api/publication/33070137 ID - 33070137 N1 - Cited By :1 Export Date: 7 October 2022 Correspondence Address: Tretter, L.; Department of Biochemistry, Hungary; email: tretter.laszlo@med.semmelweis-univ.hu Funding details: Semmelweis Egyetem, STIA-OTKA-2021, TKP2021-EGA-25 Funding details: Nemzeti Kutatási, Fejlesztési és Innovaciós Alap, NKFIA, EFOP-3.6.3-VEKOP-16-2017-00009 Funding text 1: This research was funded by the Hungarian Brain Research Program 2 (2017-1.2.1-NKP-2017-00002 to Vera Adam-Vizi, Semmelweis University), STIA-OTKA-2021 grant (from the Semmelweis University, to A.A.), TKP2021-EGA-25 grant to A.A. and C.C., Project no. TKP2021-EGA-25 has been implemented with the support provided by the Ministry of Innovation and Technology of Hungary from the National Research, Development and Innovation Fund, financed under the TKP2021-EGA funding scheme. EFOP-3.6.3-VEKOP-16-2017-00009 support to G.S. AB - α-ketoglutarate dehydrogenase complex (KGDHc), or 2-oxoglutarate dehydrogenase complex (OGDHc) is a rate-limiting enzyme in the tricarboxylic acid cycle, that has been identified in neurodegenerative diseases such as in Alzheimer’s disease. The aim of the present study was to establish the role of the KGDHc and its subunits in the bioenergetics and reactive oxygen species (ROS) homeostasis of brain mitochondria. To study the bioenergetic profile of KGDHc, genetically modified mouse strains were used having a heterozygous knock out (KO) either in the dihydrolipoyl succinyltransferase (DLST+/−) or in the dihydrolipoyl dehydrogenase (DLD+/−) subunit. Mitochondrial oxygen consumption, hydrogen peroxide (H2O2) production, and expression of antioxidant enzymes were measured in isolated mouse brain mitochondria. Here, we demonstrate that the ADP-stimulated respiration of mitochondria was partially arrested in the transgenic animals when utilizing α-ketoglutarate (α-KG or 2-OG) as a fuel substrate. Succinate and α-glycerophosphate (α-GP), however, did not show this effect. The H2O2 production in mitochondria energized with α-KG was decreased after inhibiting the adenine nucleotide translocase and Complex I (CI) in the transgenic strains compared to the controls. Similarly, the reverse electron transfer (RET)-evoked H2O2 formation supported by succinate or α-GP were inhibited in mitochondria isolated from the transgenic animals. The decrease of RET-evoked ROS production by DLST+/− or DLD+/− KO-s puts the emphasis of the KGDHc in the pathomechanism of ischemia-reperfusion evoked oxidative stress. Supporting this notion, expression of the antioxidant enzyme glutathione peroxidase was also decreased in the KGDHc transgenic animals suggesting the attenuation of ROS-producing characteristics of KGDHc. These findings confirm the contribution of the KGDHc to the mitochondrial ROS production and in the pathomechanism of ischemia-reperfusion injury. LA - English DB - MTMT ER - TY - GEN AU - Kokas, Márton AU - Sváb, Gergely AU - Tretter, László TI - A metilénkék hatása a citokróm-c redox állapotára in vivo és in vitro körülmények között PY - 2021 UR - https://m2.mtmt.hu/api/publication/34036737 ID - 34036737 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Sváb, Gergely AU - Kokas, Márton AU - Sipos, Ildikó AU - Ambrus, Attila AU - Tretter, László TI - Methylene Blue Bridges the Inhibition and Produces Unusual Respiratory Changes in Complex III-Inhibited Mitochondria. Studies on Rats, Mice and Guinea Pigs JF - ANTIOXIDANTS J2 - ANTIOXIDANTS-BASEL VL - 10 PY - 2021 IS - 2 PG - 18 SN - 2076-3921 DO - 10.3390/antiox10020305 UR - https://m2.mtmt.hu/api/publication/31887594 ID - 31887594 N1 - Funding details: KTIA_13_NAP-A-III/6 Funding details: 61826 690289, 61830Z0100 Funding details: Hungarian Scientific Research Fund, OTKA, NK 112230 Funding details: Magyar Tudományos Akadémia, MTA, MTA TKI 02001 Funding text 1: Funding: This research was funded by grants from the Hungarian Brain Research Program (KTIA_13_NAP-A-III/6 and 2017-1.2.1-NKP-2017-00002), OTKA (NK 112230), Hungarian Academy of Sciences (MTA TKI 02001) [all to Vera Adam-Vizi], and Hungarian Higher Education Institution Excellence Program (FIKP grants 61826 690289 EATV and 61830Z0100 EATV) [to A.A.]. LA - English DB - MTMT ER - TY - JOUR AU - Mikulás, Krisztina Ágnes AU - Komlódi, Tímea AU - Földes, Anna AU - Sváb, Gergely AU - Horváth, Gergő AU - Nagy, Ádám Miklós AU - Ambrus, Attila AU - Gyulai-Gaál, Szabolcs AU - Gera, István AU - Hermann, Péter AU - Varga, Gábor AU - Tretter, László TI - Bioenergetic impairment of triethylene glycol dimethacrylate- (TEGDMA-) treated dental pulp stem cells (DPSCs) and isolated brain mitochondria are amended by redox compound methylene blue JF - MATERIALS J2 - MATERIALS VL - 13 PY - 2020 IS - 16 PG - 19 SN - 1996-1944 DO - 10.3390/ma13163472 UR - https://m2.mtmt.hu/api/publication/31595275 ID - 31595275 N1 - Funding Agency and Grant Number: Hungarian Brain Research Program [KTIA_13_NAP-A-III/6, 2017-1.2.1-NKP-2017-00002]; OTKAOrszagos Tudomanyos Kutatasi Alapprogramok (OTKA) [NK 112230]; Hungarian Academy of SciencesHungarian Academy of Sciences [MTA TKI 02001]; Hungarian Human Resources Development Operational Program [EFOP-3.6.2-16-2017-00006]; Competition of Faculty of Dentistry, Semmelweis University; Higher Education Institutional Excellence Programme of the Ministry for Innovation and Technology in Hungary of the Semmelweis University [FIKP 61826 690289 EATV] Funding text: This work was supported by grants to the Hungarian Brain Research Program (KTIA_13_NAP-A-III/6 and 2017-1.2.1-NKP-2017-00002), OTKA (NK 112230), and the Hungarian Academy of Sciences (MTA TKI 02001), all to Vera Adam-Vizi, Hungarian Human Resources Development Operational Program (EFOP-3.6.2-16-2017-00006) to Gabor Varga and Anna Foldes, Competition of Faculty of Dentistry, Semmelweis University 2016 to Krisztina Mikulas. "The research was also financed by the Higher Education Institutional Excellence Programme of the Ministry for Innovation and Technology in Hungary, within the framework of the Neurology thematic programme of the Semmelweis University to Attila Ambrus (FIKP 61826 690289 EATV). AB - Background: Triethylene glycol dimethacrylate (TEGDMA) monomers released from resin matrix are toxic to dental pulp cells, induce apoptosis, oxidative stress and decrease viability. Recently, mitochondrial complex I (CI) was identified as a potential target of TEGDMA. In isolated mitochondria supported by CI, substrates oxidation and ATP synthesis were inhibited, reactive oxygen species production was stimulated. Contrary to that, respiratory Complex II was not impaired by TEGDMA. The beneficial effects of electron carrier compound methylene blue (MB) are proven in many disease models where mitochondrial involvement has been detected. In the present study, the bioenergetic effects of MB on TEGDMA-treated isolated mitochondria and on human dental pulp stem cells (DPSC) were analyzed. Methods: Isolated mitochondria and DPSC were acutely exposed to low millimolar concentrations of TEGDMA and 2 μM concentration of MB. Mitochondrial and cellular respiration and glycolytic flux were measured by high resolution respirometry and by Seahorse XF extracellular analyzer. Mitochondrial membrane potential was measured fluorimetrically. Results: MB partially restored the mitochondrial oxidation, rescued membrane potential in isolated mitochondria and significantly increased the impaired cellular O2 consumption in the presence of TEGDMA. Conclusion: MB is able to protect against TEGDMA-induced CI damage, and might provide protective effects in resin monomer exposed cells. © 2020 by the authors. LA - English DB - MTMT ER - TY - JOUR AU - Saskői, Éva AU - Hujber, Zoltán AU - Nyírő, Gábor AU - Likó, István AU - Mátyási, Barbara AU - Petővári, Gábor AU - Mészáros, Katalin AU - Kovács, Attila Lajos AU - Patthy, László AU - Supekar, Shreyas AU - Fan, Hao AU - Sváb, Gergely AU - Tretter, László AU - Sarkar, Arunabh AU - Nazir, Aamir AU - Sebestyén, Anna AU - Patócs, Attila Balázs AU - Mehta, Anil AU - Vellainé Takács, Krisztina TI - The SDHB Arg230His mutation causing familial paraganglioma alters glycolysis in a new Caenorhabditis elegans model JF - DISEASE MODELS & MECHANISMS J2 - DIS MODEL MECH VL - 13 PY - 2020 IS - 10 PG - 15 SN - 1754-8403 DO - 10.1242/dmm.044925 UR - https://m2.mtmt.hu/api/publication/31523868 ID - 31523868 N1 - These authors contributed equally to this work: Anil Mehta and Krisztina Takács-Vellai LA - English DB - MTMT ER - TY - JOUR AU - Saskői, Éva AU - Hujber, Zoltán AU - Likó, István AU - Meszaros, Katalin AU - Sarkadi, Balázs AU - Mátyási, Barbara AU - Kovács, Attila Lajos AU - Patthy, Laszlo AU - Nyírő, Gábor AU - Sváb, Gergely AU - Tretter, Laszlo AU - Mehta, Anil AU - Sebestyen, Anna AU - Patócs, Attila Balázs AU - Vellainé Takács, Krisztina TI - The Arg244His missense mutation in SDHB-1 leads to altered metabolism in Caenorhabditis elegans: a new disease model JF - ENDOCRINE ABSTRACTS J2 - ENDOCR ABSTR VL - 63 PY - 2019 PG - 1 SN - 1470-3947 DO - 10.1530/endoabs.63.P444 UR - https://m2.mtmt.hu/api/publication/30677034 ID - 30677034 LA - English DB - MTMT ER - TY - JOUR AU - Sváb, Gergely AU - Dóczi, Judit AU - Gerencsér, Ákos AU - Ambrus, Attila AU - Gallyas, Ferenc AU - Sümegi, Balázs AU - Tretter, László TI - The Mitochondrial Targets of Neuroprotective Drug Vinpocetine on Primary Neuron Cultures, Brain Capillary Endothelial Cells, Synaptosomes, and Brain Mitochondria JF - NEUROCHEMICAL RESEARCH J2 - NEUROCHEM RES VL - 44 PY - 2019 IS - 10 SP - 2435 EP - 2447 PG - 13 SN - 0364-3190 DO - 10.1007/s11064-019-02871-9 UR - https://m2.mtmt.hu/api/publication/30810275 ID - 30810275 AB - Vinpocetine is considered as neuroprotectant drug and used for treatment of brain ischemia and cognitive deficiencies for decades. A number of enzymes, channels and receptors can bind vinpocetine, however the mechanisms of many effects' are still not clear. The present study investigated the effects of vinpocetine from the mitochondrial bioenergetic aspects. In primary brain capillary endothelial cells the purinergic receptor-stimulated mitochondrial Ca2+ uptake and efflux were studied. Vinpocetine exerted a partial inhibition on the mitochondrial calcium efflux. In rodent brain synaptosomes vinpocetine (30 μM) inhibited respiration in uncoupler stimulated synaptosomes and decreased H2O2 release from the nerve terminals in resting and in complex I inhibited conditions, respectively. In isolated rat brain mitochondria using either complex I or complex II substrates leak respiration was stimulated, but ADP-induced respiration was inhibited by vinpocetine. The stimulation of oxidation was associated with a small extent of membrane depolarization. Mitochondrial H2O2 production was inhibited by vinpocetine under all conditions investigated. The most pronounced effects were detected with the complex II substrate succinate. Vinpocetine also mitigated both Ca2+-induced mitochondrial Ca2+-release and Ca2+-induced mitochondrial swelling. It lowered the rate of mitochondrial ATP synthesis, while increasing ATPase activity. These results indicate more than a single mitochondrial target of this vinca alkaloid. The relevance of the affected mitochondrial mechanisms in the anti ischemic effect of vinpocetine is discussed. LA - English DB - MTMT ER - TY - CHAP AU - Sváb, Gergely AU - Tretter, László AU - Szederkényi, Gábor ED - Vassányi, István TI - Modeling of phenylalanine metabolism and its medical relevance T2 - Proceedings of the Pannonian Conference on Advances in Information Technology (PCIT'2019) PB - University of Pannonia, Faculty of Information Technology CY - Veszprém SN - 9789633961278 PY - 2019 SP - 49 EP - 58 PG - 10 UR - https://m2.mtmt.hu/api/publication/30878884 ID - 30878884 LA - English DB - MTMT ER - TY - CHAP AU - Sváb, Gergely AU - Szederkényi, Gábor AU - Horváth, G AU - Tretter, László ED - Breitenecke, Felix ED - Kemmetmüller, Wolfgang ED - Körner, Andreas ED - Kugi, Andreas ED - Troch, Inge TI - A Simple Dynamic Model for Mitochondrial Metabolism T2 - MATHMOD 2018 Extended Abstract Volume PB - ARGESIM CY - Bécs SN - 9783901608919 T3 - ARGESIM report ; 55. PY - 2018 SP - 11 EP - 12 PG - 2 UR - https://m2.mtmt.hu/api/publication/3412404 ID - 3412404 LA - English DB - MTMT ER - TY - CHAP AU - Sváb, Gergely AU - Horváth, G AU - Szederkényi, Gábor TI - Modeling of the Citric Acid Cycle and its Two Shuttle Systems T2 - MED 2018 PB - IEEE CY - Piscataway (NJ) SN - 153867890X PY - 2018 SP - 70 EP - 77 PG - 8 DO - 10.1109/MED.2018.8442579 UR - https://m2.mtmt.hu/api/publication/3412391 ID - 3412391 LA - English DB - MTMT ER - TY - JOUR AU - Sváb, Gergely AU - Szederkényi, Gábor TI - Dynamical modeling of the most important pathways in cellular metabolism JF - JEDLIK LABORATORIES REPORTS J2 - JEDLIK LABOR REP VL - 5 PY - 2017 IS - 3 SP - 1 EP - 24 PG - 24 SN - 2064-3942 UR - https://m2.mtmt.hu/api/publication/30882909 ID - 30882909 LA - English DB - MTMT ER -