TY  - CONF
AU  - Kokas, Márton
AU  - Horváth, Gergő
AU  - Tretter, László
TI  - AZ α-KETOGLUTARÁT-DEHIDROGENÁZ KOMPLEX DLST+/- ÉS DLD+/- ALEGYSÉGEK KIÜTÉSÉNEK HATÁSA AZ OXIGÉNFOGYASZTÁSRA ÉS REAKTÍV OXIGÉNGYÖKKÉPZŐDÉSRE EGÉR AGYI MITOKONDRIUMOKON
T2  - 51. Membrán-Transzport Konferencia
PY  - 2022
UR  - https://m2.mtmt.hu/api/publication/34030854
ID  - 34030854
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  - JOUR
AU  - Daradics, Noémi
AU  - Horváth, Gergő
AU  - Tretter, László
AU  - Paál, Ágnes
AU  - Fülöp, András
AU  - Budai, András
AU  - Szijártó, Attila
TI  - The effect of Cyclophilin D depletion on liver regeneration following associating liver partition and portal vein ligation for staged hepatectomy
JF  - PLOS ONE
J2  - PLOS ONE
VL  - 17
PY  - 2022
IS  - 7
PG  - 15
SN  - 1932-6203
DO  - 10.1371/journal.pone.0271606
UR  - https://m2.mtmt.hu/api/publication/32989211
ID  - 32989211
N1  - These authors contributed equally to this work: Andras Budai, Attila Szijarto
AB  - Associating Liver Partition and Portal vein ligation for Staged hepatectomy (ALPPS) is a modification of two-stage hepatectomy profitable for patients with inoperable hepatic tumors by standard techniques. Unfortunately, initially poor postoperative outcome was associated with ALPPS, in which mitochondrial dysfunction played an essential role. Inhibition of cyclophilins has been already proposed to be efficient as a mitochondrial therapy in liver diseases. To investigate the effect of Cyclophilin D (CypD) depletion on mitochondrial function, biogenesis and liver regeneration following ALPPS a CypD knockout (KO) mice model was created.Male wild type (WT) (n = 30) and CypD KO (n = 30) mice underwent ALPPS procedure. Animals were terminated pre-operatively and 24, 48, 72 or 168 h after the operation. Mitochondrial functional studies and proteomic analysis were performed. Regeneration rate and mitotic activity were assessed.The CypD KO group displayed improved mitochondrial function, as both ATP production (P < 0.001) and oxygen consumption (P < 0.05) were increased compared to the WT group. The level of mitochondrial biogenesis coordinator peroxisome proliferator-activated receptor γ co-activator 1-α (PGC1-α) was also elevated in the CypD KO group (P < 0.001), which resulted in the induction of the mitochondrial oxidative phosphorylation system. Liver growth increased in the CypD KO group compared to the WT group (P < 0.001).Our study demonstrates the beneficial effect of CypD depletion on the mitochondrial vulnerability following ALPPS. Based on our results we propose that CypD inhibition should be further investigated as a possible mitochondrial therapy following ALPPS.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Fard-Aghaie, Mohammed-Hossein
AU  - Budai, András
AU  - Daradics, Noémi
AU  - Horváth, Gergő
AU  - Oldhafer, Karl
AU  - Szijártó, Attila
AU  - Fülöp, András
TI  - The effects of physical prehabilitation: Improved liver regeneration and mitochondrial function after ALPPS operation in a rodent model
JF  - JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES
J2  - J HEPATO-BIL-PAN SCI
VL  - 28
PY  - 2021
IS  - 8
SP  - 692
EP  - 702
PG  - 11
SN  - 1868-6974
DO  - 10.1002/jhbp.945
UR  - https://m2.mtmt.hu/api/publication/32175343
ID  - 32175343
N1  - Fard- Aghaie and Budai contributed equally to this article
AB  - Background: To identify the role of physical prehabilitation (PP) in liver regeneration, mitochondrial function, biogenesis, and inflammatory response was investigated after associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) in a rodent model. Methods: Male Wistar rats (n = 60) underwent ALPPS. Animals were divided (n = 30) to the physical prehabilitation group (PP) and sedentary group (S). The animals were exsanguinated before (0 hour) and 24, 48, 72, or 168 hours after the operation. Regeneration rate and proliferation index were assessed. Mitochondrial function, biogenesis, and inflammatory response were evaluated. Results: Regeneration rate and Ki67 index were significantly increased in the PP group compared to the S group (P <.001). Due to the changes in oxidative capacity and ATP production rate, the P/O ratio of PP group compared to the S group was significantly increased (P <.05). PP group was characterized by accelerated mitochondrial biogenesis and less intense inflammatory response compared to the S group. Conclusions: To our knowledge, this is the first demonstration of the beneficial effects of PP on liver regeneration, mitochondrial function, biogenesis, and the inflammatory response after ALPPS. © 2021 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery
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  - Tóth, Emese
AU  - Maléth, József
AU  - Závogyán, Noémi
AU  - Fanczal, Júlia
AU  - Grassalkovich, Anna
AU  - Erdős, Réka
AU  - Pallagi, Petra
AU  - Horváth, Gergő
AU  - Tretter, László
AU  - Bálint, Emese Réka
AU  - Rakonczay, Zoltán
AU  - Venglovecz, Viktória
AU  - Hegyi, Péter
TI  - Novel mitochondrial transition pore inhibitor N-methyl-4-isoleucine cyclosporin is a new therapeutic option in acute pancreatitis
JF  - JOURNAL OF PHYSIOLOGY-LONDON
J2  - J PHYSIOL-LONDON
VL  - 597
PY  - 2019
IS  - 24
SP  - 5879
EP  - 5898
PG  - 20
SN  - 0022-3751
DO  - 10.1113/JP278517
UR  - https://m2.mtmt.hu/api/publication/30857506
ID  - 30857506
N1  - First Department of Medicine, University of Szeged, Szeged, Hungary            
            Momentum Translational Gastroenterology Research Group, Hungarian Academy of Sciences–University of Szeged, Szeged, Hungary            
            Momentum Epithelial Cell Signalling and Secretion Research Group, Hungarian Academy of Sciences–University of Szeged, Szeged, Hungary            
            Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary            
            Department of Pathophysiology, University of Szeged, Szeged, Hungary            
            Department of Pharmacology and Pharmacotherapy, University of Szeged, Szeged, Hungary            
            Institute for Translational Medicine and First Department of Medicine, University of Pécs, Pécs, Hungary            
            Szentágothai Research Centre, University of Pécs, Pécs, Hungary            
            Cited By :18            
            Export Date: 26 January 2024            
            CODEN: JPHYA            
            Correspondence Address: Hegyi, P.; Momentum Translational Gastroenterology Research Group, Hungary; email: hegyi2009@gmail.com
AB  - •Bile acids, ethanol and fatty acids deteriorate pancreatic ductal fluid and bicarbonate secretion via mitochondrial damage, ATP depletion and calcium overload. •It is known that pancreatitis inducing factors open the membrane transition pore (mPTP) channel via cyclophilin D activation in acinar cells causing calcium overload and cell death and genetic or pharmacological inhibition of mPTP improves the outcome of acute pancreatitis in animal models. •In our study we show that genetic and pharmacological inhibition of mPTP protects mitochondrial homeostasis and cell function evoked by pancreatitis-inducing factors in pancreatic ductal cells. •Our results also reveal that the novel Cyclosporin A derivative NIM811 protects mitochondrial function in acinar and ductal cells, moreover it preserves bicarbonate transport mechanisms in pancreatic ductal cells. •We found that NIM811 is highly effective in different experimental pancreatitis models and that NIM811 has no side-effects. NIM811 is a highly suitable compound to be tested in clinical trials .Background and aims Mitochondrial dysfunction plays a crucial role in the development of acute pancreatitis (AP); however, no compound is currently available with clinically acceptable effectiveness and safety. In this study, we investigated the effects of a novel mitochondrial transition pore inhibitor, N-methyl-4-isoleucine cyclosporin (NIM811), in AP. Methods Pancreatic ductal and acinar cells were isolated by enzymatic digestion from Bl/6 mice. In vitro measurements were performed by confocal microscopy and microfluorometry. Preventive effects of pharmacological (cylosporin A (2 µM), NIM811 (2 µM)) or genetic (Ppif-/- /Cyp D KO) inhibition of the mitochondrial transition pore (mPTP) during the administration of either bile acids (BA) or ethanol + fatty acids (EtOH+FA) were examined. Toxicity of mPTP inhibition was investigated by detecting apoptosis and necrosis. In vivo effects of the most promising compound, NIM811 (5 or 10 mg/kg per os), were checked in three different AP models induced by either caerulein (10 × 50 µg/kg), ethanol+ fatty acid (1.75 g/kg ethanol and 750 mg/kg palmitic acid) or 4% taurocholic acid (2 ml/kg). Results Both genetic and pharmacological inhibition of Cyp D significantly prevented the toxic effects of BA and EtOH+FA by restoring mitochondrial membrane potential (Δψ) and preventing the loss of mitochondrial mass. In vivo experiments revealed that per os administration of NIM811 has a protective effect in AP by reducing oedema, necrosis, leukocyte infiltration and serum amylase level in AP models. Administration of NIM811 had no toxic effects. Conclusion The novel mitochondrial transition pore inhibitor NIM811 seems to be an exceptionally good candidate compound for clinical trials in AP. This article is protected by copyright. All rights reserved.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Chinopoulos, Christos
AU  - Batzios, S.
AU  - van, den Heuvel L.P.
AU  - Rodenburg, R.
AU  - Smeets, R.
AU  - Waterham, H.R.
AU  - Turkenburg, M.
AU  - Ruiter, J.P.
AU  - Wanders, R.J.A.
AU  - Dóczi, Judit
AU  - Horváth, Gergő
AU  - Dobolyi, Árpád
AU  - Vargiami, E.
AU  - Wevers, R.A.
AU  - Zafeiriou, D.
TI  - Mutated SUCLG1 causes mislocalization of SUCLG2 protein, morphological alterations of mitochondria and an early-onset severe neurometabolic disorder
JF  - MOLECULAR GENETICS AND METABOLISM
J2  - MOL GENET METAB
VL  - 126
PY  - 2019
IS  - 1
SP  - 43
EP  - 52
PG  - 10
SN  - 1096-7192
DO  - 10.1016/j.ymgme.2018.11.009
UR  - https://m2.mtmt.hu/api/publication/30331427
ID  - 30331427
N1  - Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary            
            1st Department of Pediatrics, “Hippokratio” General Hospital, Aristotle University, Thessaloniki, Greece            
            Department of Paediatric Metabolic Medicine, Great Ormond Street Hospital, London, United Kingdom            
            Department of Pediatrics, Radboud University Medical Centre, Nijmegen, Netherlands            
            Translational Metabolic Laboratory, Department Laboratory Medicine, Radboud University Medical Centre, Nijmegen, Netherlands            
            Laboratory Genetic Metabolic Diseases, Amsterdam University Medical Centers, University of Amsterdam, Netherlands            
            MTA-ELTE Laboratory of Molecular and Systems Neurobiology, Department of Physiology and Neurobiology, Hungarian Academy of Sciences, Eotvos Lorand University, Budapest, Hungary            
            Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary            
            Cited By :8            
            Export Date: 9 September 2021            
            CODEN: MGMEF            
            Correspondence Address: Zafeiriou, D.; 1st Department of Pediatrics, Greece; email: zafeiriou@icloud.com
Funding Agency and Grant Number: National Brain Program [NKFIH-4300-1/2017-NKP_17];  [FIKP-61822-64888-EATV];  [VEKOP 2.3.3-15-2016-00012];  [2017-2.3.4-TET-RU-2017-00003]
            Funding text: The authors thank Drs. Torocsik Beata and Patocs Attila for helpful discussions, and Drs. Joel Smet and Rudy van Coster for initial laboratory work. This work was supported by NKFIH-4300-1/2017-NKP_17 National Brain Program to A.D. and grants FIKP-61822-64888-EATV, VEKOP 2.3.3-15-2016-00012 and 2017-2.3.4-TET-RU-2017-00003 to C.C.
AB  - Succinate-CoA ligase (SUCL) is a heterodimer consisting of an alpha subunit encoded by SUCLG1, and a beta subunit encoded by either SUCLA2 or SUCLG2 catalyzing an ATP- or GTP-forming reaction, respectively, in the mitochondrial matrix. The deficiency of this enzyme represents an encephalomyopathic form of mtDNA depletion syndromes. We describe the fatal clinical course of a female patient with a pathogenic mutation in SUCLG1 (c.626C > A, p.A1a209G1u) heterozygous at the genomic DNA level, but homozygous at the transcriptional level. The patient exhibited early-onset neurometabolic abnormality culminating in severe brain atrophy and dystonia leading to death by the age of 3.5 years. Urine and plasma metabolite profiling was consistent with SUCL deficiency which was confirmed by enzyme analysis and lack of mitochondrial substrate-level phosphorylation (mSLP) in skin fibroblasts. Oxygen consumption- but not extracellular acidification rates were altered only when using glutamine as a substrate, and this was associated with mild mtDNA depletion and no changes in ETC activities. Immunoblot analysis revealed no detectable levels of SUCLG1, while SUCLA2 and SUCLG2 protein expressions were largely reduced. Confocal imaging of triple immunocytochemistry of skin fibroblasts showed that SUCLG2 co-localized only partially with the mitochondria] network which otherwise exhibited an increase in fragmentation compared to control cells. Our results outline the catastrophic consequences of the mutated SUCLG1 leading to strongly reduced SUCL activity, mSLP impairment, mislocalization of SUCLG2, morphological alterations in mitochondria and clinically to a severe neurometabolic disease, but in the absence of changes in mtDNA levels or respiratory complex activities.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Budai, András
AU  - Horváth, Gergő
AU  - Tretter, László
AU  - Radák, Zsolt
AU  - Koltai, Erika
AU  - Bori, Zoltán
AU  - Torma, Ferenc Gergely
AU  - Lukáts, Ákos
AU  - Röhlich, Pál
AU  - Szijártó, Attila
AU  - Fülöp, András
TI  - Mitochondrial function after associating liver partition and portal vein ligation for staged hepatectomy in an experimental model
JF  - BRITISH JOURNAL OF SURGERY
J2  - BRIT J SURG
VL  - 106
PY  - 2019
IS  - 1
SP  - 120
EP  - 131
PG  - 12
SN  - 0007-1323
DO  - 10.1002/bjs.10978
UR  - https://m2.mtmt.hu/api/publication/3426954
ID  - 3426954
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Fischer, Michael J.
AU  - Horváth, Gergő
AU  - Krismer, Martin
AU  - Gnaiger, Erich
AU  - Goebel, Georg
AU  - Pesta, Dominik H.
TI  - Evaluation of mitochondrial function in chronic myofascial trigger points - a prospective cohort pilot study using high-resolution respirometry
JF  - BMC MUSCULOSKELETAL DISORDERS
J2  - BMC MUSCULOSKEL DIS
VL  - 19
PY  - 2018
PG  - 9
SN  - 1471-2474
DO  - 10.1186/s12891-018-2307-0
UR  - https://m2.mtmt.hu/api/publication/30583161
ID  - 30583161
AB  - BackgroundMyofascial trigger points (MTrPs) are hyperirritable areas in the fascia of the affected muscle, possibly related to mitochondrial impairment. They can result in pain and hypoxic areas within the muscle. This pilot study established a minimally invasive biopsy technique to obtain high-quality MTrP tissue samples to evaluate mitochondrial function via high-resolution respirometry. Secondary objectives included the feasibility and safety of the biopsy procedure.MethodsTwenty healthy males participated in this study, 10 with a diagnosis of myofascial pain in the musculus (m.) trapezius MTrP (TTP group) and 10 with a diagnosis of myofascial pain in the m. gluteus medius (GTP group). Each participant had 2 muscle biopsies taken in one session. The affected muscle was biopsied followed by a biopsy from the m.vastus lateralis to be used as a control. Measurements of oxygen consumption were carried out using high-resolution respirometry.ResultsMitochondrial respiration was highest in the GTP group compared to the TTP group and the control muscle whereas no differences were observed between the GTP and the control muscle. When normalizing respiration to an internal reference state, there were no differences between muscle groups. None of the participants had hematomas or reported surgical complications. Patient-reported pain was minimal for all 3 groups. All participants reported a low procedural burden.ConclusionsThis pilot study used a safe and minimally invasive technique for obtaining biopsies from MTrPs suitable for high-resolution respirometry analysis of mitochondrial function. The results suggest that there are no qualitative differences in mitochondrial function of MTrPs of the trapezius and gluteus medius muscles compared to the vastus lateralis control muscle, implying that alterations of mitochondrial function do not appear to have a role in the development of MTrPs.Trial registrationRegistered as No. 20131128-850 at the Coordinating Center for Clinical Studies of the Medical University of Innsbruck, trial registration date: 28th November 2013 and retrospectively registered on 11th of October 2018 at ClinicalTrials.gov with the ID NCT03704311.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Hujber, Zoltán
AU  - Horváth, Gergő
AU  - Petővári, Gábor
AU  - Krencz, Ildikó
AU  - Dankó, Titanilla
AU  - Mészáros, Katalin
AU  - Rajnai, Hajnalka
AU  - Szoboszlai, Norbert
AU  - Leenders, William P J
AU  - Jeney, András
AU  - Tretter, László
AU  - Sebestyén, Anna
TI  - GABA, glutamine, glutamate oxidation and succinic semialdehyde dehydrogenase expression in human gliomas
JF  - JOURNAL OF EXPERIMENTAL AND CLINICAL CANCER RESEARCH
J2  - J EXP CLIN CANC RES
VL  - 37
PY  - 2018
IS  - 1
PG  - 12
SN  - 0392-9078
DO  - 10.1186/s13046-018-0946-5
UR  - https://m2.mtmt.hu/api/publication/30318236
ID  - 30318236
AB  - Bioenergetic characterisation of malignant tissues revealed that different tumour cells can catabolise multiple substrates as salvage pathways, in response to metabolic stress. Altered metabolism in gliomas has received a lot of attention, especially in relation to IDH mutations, and the associated oncometabolite D-2-hydroxyglutarate (2-HG) that impact on metabolism, epigenetics and redox status. Astrocytomas and oligodendrogliomas, collectively called diffuse gliomas, are derived from astrocytes and oligodendrocytes that are in metabolic symbiosis with neurons; astrocytes can catabolise neuron-derived glutamate and gamma-aminobutyric acid (GABA) for supporting and regulating neuronal functions.Metabolic characteristics of human glioma cell models - including mitochondrial function, glycolytic pathway and energy substrate oxidation - in relation to IDH mutation status and after 2-HG incubation were studied to understand the Janus-faced role of IDH1 mutations in the progression of gliomas/astrocytomas. The metabolic and bioenergetic features were identified in glioma cells using wild-type and genetically engineered IDH1-mutant glioblastoma cell lines by metabolic analyses with Seahorse, protein expression studies and liquid chromatography-mass spectrometry.U251 glioma cells were characterised by high levels of glutamine, glutamate and GABA oxidation. Succinic semialdehyde dehydrogenase (SSADH) expression was correlated to GABA oxidation. GABA addition to glioma cells increased proliferation rates. Expression of mutated IDH1 and treatment with 2-HG reduced glutamine and GABA oxidation, diminished the pro-proliferative effect of GABA in SSADH expressing cells. SSADH protein overexpression was found in almost all studied human cases with no significant association between SSADH expression and clinicopathological parameters (e.g. IDH mutation).Our findings demonstrate that SSADH expression may participate in the oxidation and/or consumption of GABA in gliomas, furthermore, GABA oxidation capacity may contribute to proliferation and worse prognosis of gliomas. Moreover, IDH mutation and 2-HG production inhibit GABA oxidation in glioma cells. Based on these data, GABA oxidation and SSADH activity could be additional therapeutic targets in gliomas/glioblastomas.
LA  - English
DB  - MTMT
ER  -