| Ethanol stimulates the production of reactive oxygen species at mitochondrial complexes I and III. | |
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MedLine Citation:
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PMID: 10515594 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The aim of this study was to investigate the hepatocellular site of reactive oxygen species generation during acute ethanol metabolism. Reactive oxygen species production was detected using the 2',7'-dichlorofluorescein fluorescence assay and cell injury was determined by lactate dehydrogenase release. Incubation with 1 and 10 mM ethanol increased the production of reactive oxygen species by 72% and 151%, respectively, which was associated with mild decreases in cell viability. Antimycin, a mitochondrial complex III inhibitor, elicited a 17-fold increase in the levels of reactive oxygen species and markedly decreased hepatocyte viability and ATP levels. Ethanol increased reactive oxygen species production and the cytosolic NADH/NAD+ ratio in antimycin-treated cells. Rotenone, a mitochondrial complex I inhibitor that allows electron flow through the flavin mononucleotide (FMN), but prevents electron flow to complex III, significantly increased reactive oxygen species production in untreated cells, but decreased reactive oxygen species production in antimycin plus ethanol-treated cells. Diphenyliodonium, a mitochondrial complex I inhibitor that inhibits electron flow through FMN, attenuated reactive oxygen species generation in all groups. Fructose prevented cytotoxicity in all treatment groups. Though they do not eliminate the participation of other intracellular compartments, these results indicate that the NADH dehydrogenase complex, as well as complex III of mitochondria, are involved in ethanol-related production of reactive oxygen species. |
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Authors:
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S M Bailey; E C Pietsch; C C Cunningham |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Free radical biology & medicine Volume: 27 ISSN: 0891-5849 ISO Abbreviation: Free Radic. Biol. Med. Publication Date: 1999 Oct |
Date Detail:
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Created Date: 1999-11-05 Completed Date: 1999-11-05 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8709159 Medline TA: Free Radic Biol Med Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 891-900 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1016, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Animals Antimycin A / analogs & derivatives, pharmacology Biphenyl Compounds / pharmacology Cell Survival / drug effects Electron Transport Complex I Electron Transport Complex III / metabolism* Ethanol / pharmacology* Fructose / pharmacology Glucose / pharmacology Male Mitochondria, Liver / drug effects* NADH, NADPH Oxidoreductases / metabolism* Onium Compounds / pharmacology Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism* Rotenone / pharmacology Uncoupling Agents / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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2887//PHS HHS; 5T32 07565//PHS HHS |
| Chemical | |
Reg. No./Substance:
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0/Biphenyl Compounds; 0/Onium Compounds; 0/Reactive Oxygen Species; 0/Uncoupling Agents; 10182-84-0/diphenyliodonium; 11118-72-2/antimycin; 30237-26-4/Fructose; 50-99-7/Glucose; 56-65-5/Adenosine Triphosphate; 64-17-5/Ethanol; 642-15-9/Antimycin A; 83-79-4/Rotenone; EC 1.10.2.2/Electron Transport Complex III; EC 1.6.-/NADH, NADPH Oxidoreductases; EC 1.6.5.3/Electron Transport Complex I |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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