A5110645973- Mitochondrial Function and Pathology
- Neonatal and fetal brain pathology
- Metabolism and Genetic Disorders
- Anesthesia and Neurotoxicity Research
- Acute Lymphoblastic Leukemia research
- Cardiac Ischemia and Reperfusion
- RNA modifications and cancer
- Neonatal Respiratory Health Research
- Fatty Acid Research and Health
- Acute Myeloid Leukemia Research
- Thyroid Disorders and Treatments
- ATP Synthase and ATPases Research
- Heme Oxygenase-1 and Carbon Monoxide
- Amino Acid Enzymes and Metabolism
- Metabolomics and Mass Spectrometry Studies
- Genetic Neurodegenerative Diseases
- Neuroscience of respiration and sleep
- Lung Cancer Treatments and Mutations
- Neurogenesis and neuroplasticity mechanisms
- Thermal Regulation in Medicine
- Parkinson's Disease Mechanisms and Treatments
- Trace Elements in Health
- Blood properties and coagulation
- Metalloenzymes and iron-sulfur proteins
- Sulfur Compounds in Biology
Rutgers, The State University of New Jersey
2022-2024
Johnson University
2022-2024
Institute of Biochemistry of Biologically Active Compounds of the National Academy of Sciences of Belarus
2023
Columbia University Irving Medical Center
2017-2021
Columbia University
2012-2021
Burke Medical Research Institute
2008-2010
Cornell University
2009-2010
National Academy of Sciences of Belarus
2007
Institute of Bioorganic Chemistry
2003
Oxidative stress and Ca 2+ toxicity are mechanisms of hypoxic–ischemic (HI) brain injury. This work investigates if partial inhibition mitochondrial respiratory chain protects HI by limiting a generation oxidative radicals during reperfusion. insult was produced in p10 mice treated with complex I (C-I) inhibitor, pyridaben, or vehicle. Administration P significantly decreased the extent Mitochondria isolated from ischemic hemisphere pyridaben-treated animals showed reduced H 2 O emission,...
Caused by a polyglutamine expansion in the huntingtin protein, Huntington's disease leads to striatal degeneration via transcriptional dysregulation of number genes, including those involved mitochondrial biogenesis. Here we show that transglutaminase 2, which is upregulated HD, exacerbates acting as selective corepressor nuclear genes; 2 interacts directly with histone H3 nucleus. In cellular model inhibition de-repressed two established regulators function, PGC-1alpha and cytochrome c...
Background and Purpose Treatment with triglyceride emulsions of docosahexaenoic acid (tri-DHA) protected neonatal mice against hypoxia-ischemia (HI) brain injury. The mechanism this neuroprotection remains unclear. We hypothesized that administration tri-DHA enriches HI-brains DHA/DHA metabolites. This reduces Ca2+-induced mitochondrial membrane permeabilization attenuates Methods 10-day-old C57BL/6J following HI-brain injury received tri-DHA, tri-EPA or vehicle. At 4–5 hours reperfusion,...
Aims: Brain ischemia/reperfusion (I/R) is associated with impairment of mitochondrial function. However, the mechanisms failure are not fully understood. This work was undertaken to determine and time course energy dysfunction after reperfusion following neonatal brain hypoxia-ischemia (HI) in mice. Results: HI/reperfusion decreased activity complex I, which recovered 30 min then declined again 1 h. Decreased I occurred parallel a loss content noncovalently bound membrane flavin...
Establishing sustained reoxygenation/reperfusion ensures not only the recovery, but may initiate a reperfusion injury in which oxidative stress plays major role. This study offers mechanism and this mechanism-specific therapeutic strategy against excessive release of reactive oxygen species (ROS) associated with reperfusion-driven recovery mitochondrial metabolism. In neonatal mice subjected to cerebral hypoxia-ischaemia (HI) reperfusion, we examined conformational changes activity complex I...
Mitochondrial dysfunction is a central feature of number acute and chronic neurodegenerative conditions, but clinically approved therapeutic interventions are only just emerging. Here we demonstrate the potential clinical utility low molecular weight inhibitors hypoxia inducible factor prolyl-4-hydroxylases (HIF PHDs) in preventing mitochondrial toxin-induced cell death mouse striatal neurons that express "knock-in" mutant Huntingtin allele. Protection from 3-nitropropionic acid (3-NP,...
Section:ChooseTop of pageAbstract <<Materials and MethodsResultsDiscussionReferencesCITING ARTICLES
Mitochondrial metabolic flux alterations are critical drivers of acute ischemia-reperfusion (IR) brain injury. Reverse electron transfer (RET), defined as the upstream flow electrons from quinone pool to complex I, is a major source pathological reactive oxygen species (ROS) under stress conditions. Using an in vivo model IR, we show that RET-supporting substrates (succinate and glycerol 3-phosphate) accumulate during deprivation. Rapid oxidation these by mitochondria upon reoxygenation...
This study demonstrates that in mice subjected to hypoxia-ischemia (HI) brain injury isoflurane anesthesia initiated upon reperfusion limits a release of mitochondrial oxidative radicals by inhibiting recovery complex-I dependent respiration. significantly attenuates an stress and reduces the extent HI injury. Neonatal were HI, at initiation exposed with or without mechanical ventilation. At end exposure cerebral respiration, H2O2 emission rates measured followed assessment damage infarct...
Nelfinavir (NLF), an antiretroviral agent, preserves mitochondrial membranes integrity and protects mature brain against ischemic injury in rodents. Our study demonstrates that neonatal mice NLF significantly limits calcium influx, the event associated with protection of hypoxic-ischemic insult (HI). Compared to vehicle-treated mice, cerebral mitochondria from NLF-treated exhibited a greater tolerance Ca2+-induced membrane permeabilization, ADP-phosphorylating activity reduced cytochrome C...
Impairments in mitochondrial energy metabolism have been implicated human genetic diseases associated with and nuclear DNA mutations, neurodegenerative cardiovascular disorders, diabetes, aging. Alteration complex I structure activity has shown to play a key role Parkinson's disease ischemia/reperfusion tissue injury, but significant difficulty remains assessing the content of this enzyme given sample. The present study introduces new method utilizing native polyacrylamide gel...
Reperfusion triggers an oxidative stress. We hypothesized that mild hypoxemia in reperfusion attenuates brain injury following hypoxia-ischemia (HI). In neonatal HI-mice, the was initiated by reoxygenation with room air (RA) followed exposure to 100%, 21%, 18%, 15% oxygen for 60 minutes. Systemic saturation (SaO 2 ), cerebral blood flow (CBF), mitochondrial respiration and permeability transition pore (mPTP) opening, markers of injury, infarcts were assessed. Compared RA-littermates, HI-mice...
Postnatal failure of oligodendrocyte maturation has been proposed as a cellular mechanism diffuse white matter injury (WMI) in premature infants. However, the molecular mechanisms for maturational remain unclear. In neonatal mice and cultured differentiating oligodendrocytes, sublethal intermittent hypoxic (IH) stress activated cyclophilin D–dependent mitochondrial proton leak uncoupled respiration, leading to transient bioenergetic stress. This was associated with development WMI: poor...
Pathologies associated with tissue ischemia/reperfusion (I/R) in highly metabolizing organs such as the brain and heart are leading causes of death disability humans. Molecular mechanisms underlying mitochondrial dysfunction during acute injury I/R tissue-specific, but their details not completely understood. A metabolic shift accumulation substrates reverse electron transfer (RET) succinate observed ischemia, making complex I respiratory chain (NADH:ubiquinone oxidoreductase) most...
The present work documents the first example of an enzyme-catalyzed β-elimination a thioether from sulfonium cysteine <i>S</i>-conjugate. β-(<i>S</i>-Tetrahydrothiophenium)-l-alanine (THT-A) is <i>S</i>-conjugate busulfan. THT-A slowly undergoes nonenzymatic reaction at pH 7.4 and 37°C to yield tetrahydrothiophene, pyruvate, ammonia. This accelerated by 1) rat liver, kidney, brain homogenates, 2) isolated liver mitochondria, 3) pyridoxal 5′-phosphate (PLP). A PLP-dependent enzyme in cytosol...
Hypothermia (HT) is a standard of care in the management hypoxic-ischemic brain injury (HI). However, therapeutic mechanisms HT are not well understood. We found that at temperature 32°C, isolated mitochondria exhibited significantly greater resistance to an opening calcium-induced permeability transition pore (mPTP), compared 37°C. Mitochondrial calcium buffering capacity (mCBC) was linearly and inversely dependent upon (25°C-37°C). Importantly, 37°C cyclosporine A did increase mCBC, but...
Thyroid cells fall into the type of functioning during continuous production high H(2)O(2) concentrations. We studied effect H(2)O(2)-induced oxidative stress (0.1, 1.0 and 10.0 mM) on activities key steps iodide metabolism (uptake, oxidation organification) in thyrocytes cultivated an organ culture. After 60 min cultivation a medium containing at concentrations mM (I(-)) uptake, thyroperoxidase (TPO) activity I(-) organification were completely inhibited. No restoration parameters was...