TY - JOUR AU - Nagy, György AU - Géher, Pál AU - Tamási, László AU - Drescher, Edit AU - Keszthelyi, Péter AU - Pulai, Judit AU - Czirják, László AU - Szekanecz, Zoltán AU - Kiss, Gergely AU - Kovács, László TI - Real-world evidence on methotrexate-free subcutaneous tocilizumab therapy in patients with rheumatoid arthritis : 24-week data from the SIMPACT study JF - RHEUMATOLOGY ADVANCES IN PRACTICE J2 - RHEUMATOL ADV PRACT VL - 6 PY - 2022 IS - 2 PG - 13 SN - 2514-1775 DO - 10.1093/rap/rkac038 UR - https://m2.mtmt.hu/api/publication/32866658 ID - 32866658 AB - The aim of the SIMPACT study was to evaluate the efficacy and safety of MTX-free s.c. tocilizumab (TCZ) therapy in RA patients.SIMPACT was an open-label, non-controlled, non-randomized, non-interventional study, in which RA patients for whom the treating physicians ordered s.c. TCZ were observed during a 24-week treatment period in Hungarian centres. Although the use of MTX was avoided during the study period, other conventional synthetic DMARDs, oral CSs and NSAIDs were allowed. Study endpoints included the change in DAS28 and clinical activity index (CDAI) scores, the proportion of patients achieving remission in the whole population and in subgroups defined based on prior RA treatment history, and age, weight or biological sex post hoc. The extent of supplementary medication use was monitored.Three hundred and thirty-seven RA patients were enrolled in 18 study centres. TCZ therapy significantly decreased the disease activity measured by both DAS28 (P = 0.0001) and CDAI (P = 0.0001). Clinical response was more pronounced in biologic-naïve patients and was lower in patients >75 years of age. In the whole population, DAS28 ESR or CRP and CDAI remission rates were 70.10%, 78.95% and 33.59%, respectively. In patients <45 years of age, the CDAI remission rate doubled (67.86%). A significant decrease in the frequency of co-administered medication was reported, including oral CSs and DMARDs.Real-world clinical evidence on s.c. TCZ reported here is in line with the efficacy outcomes of randomized clinical trials. Subgroup analysis revealed that TCZ was more effective in biologic-naïve patients and in those <75 years old.ClinicalTrials.gov, http://www.clinicaltrials.gov, NCT02402686. LA - English DB - MTMT ER - TY - JOUR AU - Starkov, AA AU - Chinopoulos, Christos AU - Starkova, NN AU - Konrád, Csaba AU - Kiss, Gergely AU - Stepanova, A AU - Popov, VN TI - Divalent cation chelators citrate and EDTA unmask an intrinsic uncoupling pathway in isolated mitochondria. JF - JOURNAL OF BIOENERGETICS AND BIOMEMBRANES J2 - J BIOENERG BIOMEMBR VL - 49 PY - 2017 IS - 1 SP - 3 EP - 11 PG - 9 SN - 0145-479X DO - 10.1007/s10863-016-9656-x UR - https://m2.mtmt.hu/api/publication/3037329 ID - 3037329 N1 - Megjegyzés-26494045 N1 Funding details: 6.149.2014/К, Minobrnauka, Ministry of Education and Science of the Russian Federation N1 Funding details: PO AG 14930, NIH, National Institutes of Health AB - We demonstrate a suppression of ROS production and uncoupling of mitochondria by exogenous citrate in Mg2+ free medium. Exogenous citrate suppressed H2O2 emission and depolarized mitochondria. The depolarization was paralleled by the stimulation of respiration of mitochondria. The uncoupling action of citrate was independent of the presence of sodium, potassium, or chlorine ions, and it was not mediated by the changes in permeability of the inner mitochondrial membrane to solutes. The citrate transporter was not involved in the citrate effect. Inhibitory analysis data indicated that several well described mitochondria carriers and channels (ATPase, IMAC, ADP/ATP translocase, mPTP, mKATP) were not involved in citrate's effect. Exogenous MgCl2 strongly inhibited citrate-induced depolarization. The uncoupling effect of citrate was demonstrated in rat brain, mouse brain, mouse liver, and human melanoma cells mitochondria. We interpreted the data as an evidence to the existence of a hitherto undescribed putative inner mitochondrial membrane channel that is regulated by extramitochondrial Mg2+ or other divalent cations. LA - English DB - MTMT ER - TY - JOUR AU - Németh, Beáta AU - Dóczi, Judit AU - Csete, Dániel AU - Kacsó, Gergely AU - Ravasz, Dóra AU - Daniel, Adams AU - Kiss, Gergely AU - Nagy, Ádám Miklós AU - Horváth, Gergő AU - Tretter, László AU - Mócsai, Attila AU - Csépányi-Kömi, Roland AU - Iordanov, Iordan AU - Ádám, Veronika AU - Chinopoulos, Christos TI - Abolition of mitochondrial substrate-level phosphorylation by itaconic acid produced by LPS-induced Irg1 expression in cells of murine macrophage lineage JF - FASEB JOURNAL J2 - FASEB J VL - 30 PY - 2016 IS - 1 SP - 286 EP - 300 PG - 15 SN - 0892-6638 DO - 10.1096/fj.15-279398 UR - https://m2.mtmt.hu/api/publication/2940351 ID - 2940351 LA - English DB - MTMT ER - TY - THES AU - Kiss, Gergely TI - The role of matrix substrate-level phosphorylation during anoxia PB - Semmelweis Egyetem PY - 2015 DO - 10.14753/SE.2015.1713 UR - https://m2.mtmt.hu/api/publication/2955220 ID - 2955220 LA - English DB - MTMT ER - TY - JOUR AU - Chinopoulos, Christos AU - Kiss, Gergely AU - Kawamata, H AU - Starkov, AA TI - Measurement of ADP-ATP Exchange in Relation to Mitochondrial Transmembrane Potential and Oxygen Consumption. JF - METHODS IN ENZYMOLOGY J2 - METHOD ENZYMOL VL - 542 PY - 2014 SP - 333 EP - 348 PG - 16 SN - 0076-6879 DO - 10.1016/B978-0-12-416618-9.00017-0 UR - https://m2.mtmt.hu/api/publication/2594473 ID - 2594473 AB - We have previously described a fluorometric method to measure ADP-ATP exchange rates in mitochondria of permeabilized cells, in which several enzymes that consume substantial amounts of ATP and other competing reactions interconverting adenine nucleotides are present. This method relies on recording changes in free extramitochondrial Mg(2+) with the Mg(2+)-sensitive fluorescent indicator Magnesium Green (MgGr), exploiting the differential affinity of ADP and ATP for Mg(2+). In particular, cells are permeabilized with digitonin in the presence of [Formula: see text] and Na3VO4, inhibiting all ATP- and ADP-utilizing reactions but mitochondrial exchange of ATP with ADP catalyzed by the adenine nucleotide translocase. The rate of ATP appearing in the medium upon the addition of ADP to energized mitochondria is then calculated from the rate of change in free extramitochondrial Mg(2+) using standard binding equations. Here, we describe a variant of this method involving an improved calibration step. This step minimizes errors that may be introduced during the conversion of the MgGr signal into free extramitochondrial [Mg(2+)] and ATP. Furthermore, we describe an approach for combining this methodology with the measurement of mitochondrial membrane potential and oxygen consumption in the same sample. The method described herein is useful for the study of malignant cells, which are known to thrive in hypoxic environments and to harbor mitochondria with profound functional alterations. LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Gergely AU - Konrád, Csaba AU - Pour-Ghaz, I AU - Mansour, JJ AU - Németh, Beáta AU - Starkov, AA AU - Ádám, Veronika AU - Chinopoulos, Christos TI - Mitochondrial diaphorases as NAD+ donors to segments of the citric acid cycle that support substrate-level phosphorylation yielding ATP during respiratory inhibition. JF - FASEB JOURNAL J2 - FASEB J VL - 28 PY - 2014 IS - 4 SP - 1682 EP - 1697 PG - 16 SN - 0892-6638 DO - 10.1096/fj.13-243030 UR - https://m2.mtmt.hu/api/publication/2497374 ID - 2497374 AB - Substrate-level phosphorylation mediated by succinyl-CoA ligase in the mitochondrial matrix produces high-energy phosphates in the absence of oxidative phosphorylation. Furthermore, when the electron transport chain is dysfunctional, provision of succinyl-CoA by the alpha-ketoglutarate dehydrogenase complex (KGDHC) is crucial for maintaining the function of succinyl-CoA ligase yielding ATP, preventing the adenine nucleotide translocase from reversing. We addressed the source of the NAD+ supply for KGDHC under anoxic conditions and inhibition of complex I. Using pharmacologic tools and specific substrates and by examining tissues from pigeon liver exhibiting no diaphorase activity, we showed that mitochondrial diaphorases in the mouse liver contribute up to 81% to the NAD+ pool during respiratory inhibition. Under these conditions, KGDHC's function, essential for the provision of succinyl-CoA to succinyl-CoA ligase, is supported by NAD+ derived from diaphorases. Through this process, diaphorases contribute to the maintenance of substrate-level phosphorylation during respiratory inhibition, which is manifested in the forward operation of adenine nucleotide translocase. Finally, we show that reoxidation of the reducible substrates for the diaphorases is mediated by complex III of the respiratory chain.-Kiss, G., Konrad, C., Pour-Ghaz, I., Mansour, J. J., Nemeth, B., Starkov, A. A., Adam-Vizi, V., Chinopoulos, C. Mitochondrial diaphorases as NAD+ donors to segments of the citric acid cycle that support substrate-level phosphorylation yielding ATP during respiratory inhibition. LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Gergely AU - Konrád, Csaba AU - Starkov, Anatoly A AU - Kawamata, Hibiki AU - Manfredi, Giovanni AU - Zhang, Steven F AU - Gibson, Gary E AU - Beal, M Flint AU - Ádám, Veronika AU - Chinopoulos, Christos TI - A reduction in the activity of alpha-ketoglutarate dehydrogenase complex decreases matrix substrate-level phosphorylation and prompts respiration-impaired mitochondria towards extramitochondrial ATP consumption JF - JOURNAL OF NEUROSCIENCE RESEARCH J2 - J NEUROSCI RES VL - 91 PY - 2013 IS - 8 SP - 1099 EP - 1100 PG - 2 SN - 0360-4012 UR - https://m2.mtmt.hu/api/publication/2528926 ID - 2528926 LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Gergely AU - Konrád, Csaba AU - Ádám, Veronika AU - Chinopoulos, Christos TI - Functional importance of mitochondrial diaphorases in maintaining phosphorylation potential during inhibition of electron transport chain. JF - JOURNAL OF NEUROSCIENCE RESEARCH J2 - J NEUROSCI RES VL - 91 PY - 2013 IS - 8 SP - 1088 EP - 1088 PG - 1 SN - 0360-4012 UR - https://m2.mtmt.hu/api/publication/2528925 ID - 2528925 N1 - 10th International Conference on Brain Energy Metabolism - Bioenergetics of Neurological Disease and Aging APR 17-20, 2012 Pacific Grove, CA LA - English DB - MTMT ER - TY - JOUR AU - Kiss, Gergely AU - Konrád, Csaba AU - Dóczi, Judit AU - Starkov, AA AU - Kawamata, H AU - Manfredi, G AU - Zhang, SF AU - Gibson, GE AU - Beal, MF AU - Ádám, Veronika AU - Chinopoulos, Christos TI - The negative impact of alpha-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation JF - FASEB JOURNAL J2 - FASEB J VL - 27 PY - 2013 IS - 6 SP - 2392 EP - 2406 PG - 15 SN - 0892-6638 DO - 10.1096/fj.12-220202 UR - https://m2.mtmt.hu/api/publication/2228167 ID - 2228167 AB - A decline in alpha-ketoglutarate dehydrogenase complex (KGDHC) activity has been associated with neurodegeneration. Provision of succinyl-CoA by KGDHC is essential for generation of matrix ATP (or GTP) by substrate-level phosphorylation catalyzed by succinyl-CoA ligase. Here, we demonstrate ATP consumption in respiration-impaired isolated and in situ neuronal somal mitochondria from transgenic mice with a deficiency of either dihydrolipoyl succinyltransferase (DLST) or dihydrolipoyl dehydrogenase (DLD) that exhibit a 20-48% decrease in KGDHC activity. Import of ATP into the mitochondrial matrix of transgenic mice was attributed to a shift in the reversal potential of the adenine nucleotide translocase toward more negative values due to diminished matrix substrate-level phosphorylation, which causes the translocase to reverse prematurely. Immunoreactivity of all three subunits of succinyl-CoA ligase and maximal enzymatic activity were unaffected in transgenic mice as compared to wild-type littermates. Therefore, decreased matrix substrate-level phosphorylation was due to diminished provision of succinyl-CoA. These results were corroborated further by the finding that mitochondria from wild-type mice respiring on substrates supporting substrate-level phosphorylation exhibited approximately 30% higher ADP-ATP exchange rates compared to those obtained from DLST+/- or DLD+/- littermates. We propose that KGDHC-associated pathologies are a consequence of the inability of respiration-impaired mitochondria to rely on "in-house" mitochondrial ATP reserves.-Kiss, G., Konrad, C., Doczi, J., Starkov, A. A., Kawamata, H., Manfredi, G., Zhang, S. F., Gibson, G. E., Beal, M. F., Adam-Vizi, V., Chinopoulos, C. The negative impact of alpha-ketoglutarate dehydrogenase complex deficiency on matrix substrate-level phosphorylation. LA - English DB - MTMT ER - TY - JOUR AU - Konrád, Csaba AU - Kiss, Gergely AU - Törőcsik, Beáta AU - Ádám, Veronika AU - Chinopoulos, Christos TI - Absence of Ca2+-induced mitochondrial permeability transition but presence of bongkrekate-sensitive nucleotide exchange in C. crangon and P. serratus JF - BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS J2 - BBA-BIOENERGETICS VL - 1817 PY - 2012 IS - Suppl. SP - S121 EP - S121 SN - 0005-2728 DO - 10.1016/j.bbabio.2012.06.325 UR - https://m2.mtmt.hu/api/publication/2529232 ID - 2529232 N1 - 17th European Bioenergetics Conference SEP 15-20, 2012 Freiburg, GERMANY LA - English DB - MTMT ER -