Document Detail


Hyperoxic sheep pulmonary microvascular endothelial cells generate free radicals via mitochondrial electron transport.
MedLine Citation:
PMID:  8380815     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Free radical generation by hyperoxic endothelial cells was studied using electron paramagnetic resonance (EPR) spectroscopy and the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Studies were performed to determine the radical species produced, whether mitochondrial electron transport was involved, and the effect of the radical generation on cell mortality. Sheep pulmonary microvascular endothelial cell suspensions exposed to 100% O2 for 30 min exhibited prominent DMPO-OH and, occasionally, additional smaller DMPO-R signals thought to arise from the trapping of superoxide anion (O2-.), hydroxyl (.OH), and alkyl (.R) radicals. Superoxide dismutase (SOD) quenched both signals suggesting that the observed radicals were derived from O2-.. Studies with deferoxamine suggested that the generation of .R occurred secondary to the formation of .OH from O2-. via an iron-mediated Fenton reaction. Blocking mitochondrial electron transport with rotenone (20 microM) markedly decreased radical generation. Cell mortality increased slightly in oxygen-exposed cells. This increase was not significantly altered by SOD or deferoxamine, nor was it different from the mortality observed in air-exposed cells. These results suggest that endothelial cells exposed to hyperoxia for 30 min produce free radicals via mitochondrial electron transport, but under the conditions of these experiments, this radical generation did not appear cause cell death.
Authors:
S P Sanders; J L Zweier; P Kuppusamy; S J Harrison; D J Bassett; E W Gabrielson; J T Sylvester
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  91     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1993 Jan 
Date Detail:
Created Date:  1993-02-24     Completed Date:  1993-02-24     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  46-52     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21224.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antimycin A / pharmacology
Cells, Cultured
Cyanides / pharmacology
Cyclic N-Oxides
Electron Spin Resonance Spectroscopy
Electron Transport / drug effects
Endothelium, Vascular / drug effects,  metabolism*
Free Radicals / metabolism
Kinetics
Lung / blood supply*
Microcirculation*
Mitochondria / drug effects,  metabolism*
Oxygen / pharmacology*
Rotenone / pharmacology
Sheep
Spin Labels
Grant Support
ID/Acronym/Agency:
HL-17655-13/HL/NHLBI NIH HHS; HL-38324/HL/NHLBI NIH HHS; HL-41970/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Cyanides; 0/Cyclic N-Oxides; 0/Free Radicals; 0/Spin Labels; 3317-61-1/5,5-dimethyl-1-pyrroline-1-oxide; 642-15-9/Antimycin A; 7782-44-7/Oxygen; 83-79-4/Rotenone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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