| Mitochondria as a source of reactive oxygen species during reductive stress in rat hepatocytes. | |
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MedLine Citation:
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PMID: 8386454 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cell killing, oxygen consumption, and hydroperoxide formation were determined in rat hepatocytes after glycolytic and respiratory inhibition. These conditions model the ATP depletion and reductive stress of anoxia ("chemical hypoxia"). Glycolysis was inhibited with iodoacetate, and mitochondrial electron transfer was blocked with sodium azide, cyanide, or myxothiazol. Cell killing, hydroperoxide formation, and inhibitor-insensitive oxygen consumption were greater after azide than after myxothiazol or cyanide. Desferrioxamine, an inhibitor of iron-catalyzed hydroxyl radical formation, delayed cell killing after each of the respiratory inhibitors. Anoxia also delayed cell killing during chemical hypoxia. However, during anoxic incubations, desferrioxamine did not delay the onset of cell death. These findings indicate that reactive oxygen species participate in lethal cell injury during chemical hypoxia. In isolated mitochondria, previous studies have shown that myxothiazol inhibits Q cycle-mediated ubisemiquinone formation in complex III (ubiquinol-cytochrome c oxidoreductase) and that ubisemiquinone can react with molecular oxygen to form superoxide. Decreased killing of hepatocytes with myxothiazol compared with azide suggests, therefore, that mitochondrial oxygen radical formation by complex III is involved in cell killing during reductive stress. In support of this hypothesis, myxothiazol reduced rates of cell killing and hydroperoxide formation in hepatocytes incubated with azide or cyanide. This mitochondrial mechanism for oxygen radical formation may be important in relative but not absolute hypoxia. |
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Authors:
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T L Dawson; G J Gores; A L Nieminen; B Herman; J J Lemasters |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The American journal of physiology Volume: 264 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1993 Apr |
Date Detail:
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Created Date: 1993-05-17 Completed Date: 1993-05-17 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: C961-7 Citation Subset: IM |
Affiliation:
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Department of Cell Biology and Anatomy, School of Medicine, University of North Carolina, Chapel Hill 27599-7090. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Azides / pharmacology Cell Death / drug effects Cell Hypoxia Cell Survival Cells, Cultured Electron Transport Complex III / antagonists & inhibitors Hydrogen Peroxide / metabolism* Kinetics Liver / cytology, drug effects, metabolism* Male Methacrylates Mitochondria, Liver / drug effects, metabolism* Models, Biological Oligomycins / pharmacology Oxygen Consumption / drug effects* Potassium Cyanide / pharmacology Rats Rats, Sprague-Dawley Sodium Azide Thiazoles / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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AG-07218/AG/NIA NIH HHS; DK-37034/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Azides; 0/Methacrylates; 0/Oligomycins; 0/Thiazoles; 151-50-8/Potassium Cyanide; 26628-22-8/Sodium Azide; 76706-55-3/myxothiazol; 7722-84-1/Hydrogen Peroxide; EC 1.10.2.2/Electron Transport Complex III |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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