A5053144324- Mitochondrial Function and Pathology
- Neuroscience and Neuropharmacology Research
- ATP Synthase and ATPases Research
- Metabolism and Genetic Disorders
- Cancer, Hypoxia, and Metabolism
- Biochemical Acid Research Studies
- Electron Spin Resonance Studies
- Ion channel regulation and function
- Photoreceptor and optogenetics research
- Cardiac Ischemia and Reperfusion
- Vitamin C and Antioxidants Research
- Metabolomics and Mass Spectrometry Studies
- Neuroinflammation and Neurodegeneration Mechanisms
- Adipose Tissue and Metabolism
- Molecular Sensors and Ion Detection
- Alcoholism and Thiamine Deficiency
- Redox biology and oxidative stress
- Free Radicals and Antioxidants
- Pancreatitis Pathology and Treatment
- Signaling Pathways in Disease
- Lipid Membrane Structure and Behavior
- Biochemical effects in animals
- Marine Toxins and Detection Methods
- Neurogenesis and neuroplasticity mechanisms
- Diet and metabolism studies
Semmelweis University
2015-2024
Institute of Biochemistry
1987-2024
Pázmány Péter Catholic University
2018
Hungarian Academy of Sciences
2006-2015
Istituto De Angeli (Italy)
2011
Google (United States)
2005
HUN-REN Institute of Experimental Medicine
1998
α-Ketoglutarate dehydrogenase (α-KGDH), a key enzyme in the Krebs' cycle, is crucial early target of oxidative stress (Tretter and Adam-Vizi, 2000). The present study demonstrates that α-KGDH able to generate H 2 O and, thus, could also be source reactive oxygen species (ROS) mitochondria. Isolated with coenzyme A (HS-CoA) thiamine pyrophosphate started produce after addition α-ketoglutarate absence nicotinamide adenine dinucleotide-oxidized (NAD + ). NAD , which proved powerful inhibitor...
In this study we addressed the function of Krebs cycle to determine which enzyme(s) limits availability reduced nicotinamide adenine dinucleotide (NADH) for respiratory chain under H(2)O(2)-induced oxidative stress, in intact isolated nerve terminals. The enzyme that was most vulnerable inhibition by H(2)O(2) proved be aconitase, being completely blocked at 50 microm H(2)O(2). alpha-Ketoglutarate dehydrogenase (alpha-KGDH) also inhibited but only higher concentrations (>/=100 microm), and...
Itaconate is a nonamino organic acid exhibiting antimicrobial effects. It has been recently identified in cells of macrophage lineage as product an enzyme encoded by immunoresponsive gene 1 (Irg1), acting on the citric cycle intermediate cis-aconitate. In mitochondria, itaconate can be converted succinate-coenzyme A (CoA) ligase to itaconyl-CoA at expense ATP (or GTP), and also weak competitive inhibitor complex II. Here, we investigated specific bioenergetic effects increased production...
Despite significant advances in our understanding of the biology determining systemic energy homeostasis, treatment obesity remains a medical challenge. Activation AMP-activated protein kinase (AMPK) has been proposed as an attractive strategy for and its complications. AMPK is conserved, ubiquitously expressed, heterotrimeric serine/threonine whose short-term activation multiple beneficial metabolic effects. Whether these translate into long-term benefits complications unknown. Here, we...
Brain injury is accompanied by neuroinflammation, accumulation of extracellular glutamate and mitochondrial dysfunction, all which cause neuronal death. The aim this study was to investigate the impact these mechanisms on Patients from neurosurgical intensive care unit suffering aneurysmal subarachnoid hemorrhage (SAH) were recruited retrospectively a respective database. In vitro experiments performed in rat cortex homogenate, primary dissociated cultures, B35 NG108-15 cell lines. We...
Abstract In this study reactive oxygen species (ROS) generated in the respiratory chain were measured and quantitative relationship between inhibition of complexes ROS formation was investigated isolated nerve terminals. We addressed to what extent complex I, III IV,respectively, should be inhibited cause generation. For IV, rotenone, antimycin cyanide used, respectively, followed by measuring activity aconitase enzyme. not detected until up 71 ± 4%, above that threshold inhibition, decrease...
Abstract: Mitochondrial membrane potential (Δ? m ) was determined in intact isolated nerve terminals using the potential‐sensitive probe JC‐1. Oxidative stress induced by H 2 O (0.1‐1 M caused only a minor decrease Δ? . When complex I of respiratory chain inhibited rotenone (2 μ ), unaltered, but on subsequent addition , started to and collapsed during incubation with 0.5 for 12 min. The ATP level [ATP]/[ADP] ratio were greatly reduced simultaneous presence also marked reduction when added...
Although incidence and prevalence of prediabetes are increasing, little is known about its cardiac effects. Therefore, our aim was to investigate the effect on function characterize parameters pathways associated with deteriorated performance. Long-Evans rats were fed either control or high-fat chow for 21 wk treated a single low dose (20 mg/kg) streptozotocin at week 4 High-fat treatment induced as characterized by slightly elevated fasting blood glucose, impaired glucose insulin tolerance,...
Abstract Characteristics of reactive oxygen species (ROS) production in isolated guinea‐pig brain mitochondria respiring on α‐glycerophosphate (α‐GP) were investigated and compared with those supported by succinate. Mitochondria established a membrane potential (ΔΨ m ) released H 2 O parallel an increase NAD(P)H fluorescence the presence α‐GP (5–40 ). formation level inhibited rotenone, ADP or FCCP, respectively, being consistent reverse electron transfer (RET). The residual FCCP was...
// Hajnalka Harami-Papp 1, * , Lőrinc S. Pongor 3, Gyöngyi Munkácsy 1 Gergő Horváth 2 Ádám M. Nagy Attila Ambrus Péter Hauser 3 András Szabó László Tretter Balázs Győrffy MTA TTK Lendület Cancer Biomarker Research Group, H-1117, Budapest, Hungary Semmelweis University, Department of Medical Biochemistry, H-1094, Second Pediatrics, These authors have contributed equally to this work Correspondence to: Győrffy,...
The redox dye methylene blue (MB) is proven to have beneficial effects in various models of neurodegenerative diseases. Here we investigated the MB (100 nM, 300 and 1 μM) on key bioenergetic parameters H2O2 production/elimination isolated guinea pig brain mitochondria under normal as well respiration-impaired conditions. As measured by high-resolution Oxygraph rate resting oxygen consumption was increased, but ADP-stimulated respiration unaffected with any substrates (glutamate malate,...
Abstract Dihydrolipoamide dehydrogenase (LADH) is a flavo‐enzyme that serves as subunit of α‐ketoglutarate complex (α‐KGDHC). Reactive oxygen species (ROS) generation by α‐KGDHC has been assigned to LADH (E3 subunit) and explained the diaphorase activity E3. Dysfunctions concurrent ROS production have implicated in neurodegeneration, ischemia‐reperfusion, other pathological conditions. In this work we investigated in‐depth details isolated α‐KGDHC. We found parallel superoxide hydrogen...
We investigated pathogenic mutations relevant in dihydrolipoamide dehydrogenase (LADH; gene: Dld) deficiency, a severe human disease, to elucidate how they alter reactive oxygen species (ROS) generation and associated biophysical characteristics of LADH. Twelve known disease-causing mutants LADH have been expressed purified homogeneity from E. coli. Detailed biochemical characterization the has performed applying circular dichroism (CD) spectroscopy, nano-spray mass spectrometry (MS),...
Herein are reported unique properties of the human 2-oxoglutarate dehydrogenase multienzyme complex (OGDHc), a rate-limiting enzyme in Krebs (citric acid) cycle. (a) Functionally competent (E1o-h) and dihydrolipoyl succinyltransferase components have been expressed according to kinetic spectroscopic evidence. (b) A stable free radical, consistent with C2-(C2α-hydroxy)-γ-carboxypropylidene thiamin diphosphate (ThDP) cation radical was detected by electron spin resonance upon reaction E1o-h...
We have explored the consequences of a [Na(+)](i) load and oxidative stress in isolated nerve terminals. The Na(+) was achieved by veratridine (5-40 microM), which allows entry via voltage-operated channel, induced hydrogen peroxide (0.1-0.5 mM). Remarkably, neither nor exposure to H(2)O(2) had any major effect on [Ca(2+)](i), mitochondrial membrane potential (Deltapsim), or ATP level. However, combination an caused depletion, collapse Deltapsim, progressive deregulation [Ca(2+)](i)...
The Warburg effect occurs both in cancer cells and inflammatory macrophages. aim of our work was to demonstrate the role PI3K-Akt-mTOR axis HL-60 derived, rat peritoneal human blood macrophages investigate potential selected inhibitors this pathway antagonize it. M1 polarization HL-60-derived monocyte-derived supported by increased expression NOS2 cytokines. All polarized investigated expressed higher levels HIF-1α NOS2, which were reduced kinase inhibitors, supporting axis. Using Seahorse...
Abstract Earlier reports that generation of reactive oxygen species (ROS) by isolated mitochondria supported succinate was sensitive to small changes in the mitochondrial membrane potential (ΔΨm) served as a basis for concept ‘mild uncoupling’ suggesting few millivolts decrease ΔΨm would be beneficial neuroprotection because reducing production ROS mitochondria. In this study, we tested whether situ mitochondria, which function normal cytosolic environment and oxidize glucose‐derived...