Document Detail

Chronic hypoxia, glutathione-dependent detoxication, and metabolic instability in rat small intestine.
MedLine Citation:
PMID:  9124357     Owner:  NLM     Status:  MEDLINE    
We previously showed that chronic hypoxia decreases activity of intestinal glutathione (GSH)-dependent enzymes and is associated with a proximal-to-distal gradient of enzyme activity, suggesting reduced detoxication capacity in ileal cells. To assess whether hypoxia affects metabolism of hydroperoxides, jejunal and ileal enterocytes from rats exposed to air (n = 11) or 10% O2 (n = 9) for 10 days were exposed to 300 microM tert-butyl hydroperoxide (t-BH). The initial rate of hydroperoxide metabolism was 50-90% faster in hypoxic enterocytes, but cell killing was enhanced. Metabolism in normoxic, but not hypoxic, cells was enhanced threefold by addition of 10 mM glucose. Hypoxic enterocytes exhibited a higher baseline GSH/GSH disulfide (GSSG) ratio but a larger percent decrease after t-BH exposure. t-BH induced a 35-40% decrease in protein-bound sulfhydryl groups in normoxic and hypoxic enterocytes, but protein-bound sulfhydryl was protected by glucose in normoxic cells only. Metabolic response to substrate load or hydroperoxide challenge was assessed by measurement of cellular O2 consumption. Hypoxia, but not normoxia, increases and decreases O2 consumption on exposure to glucose and oxidant, respectively, suggesting metabolic dysregulation. In summary, prolonged O2 deficiency induces loss of intestinal metabolic integrity that is associated with altered peroxide detoxication activity and mitochondrial respiratory function.
T S LeGrand; T Y Aw
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of physiology     Volume:  272     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1997 Feb 
Date Detail:
Created Date:  1997-04-24     Completed Date:  1997-04-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370511     Medline TA:  Am J Physiol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  G328-34     Citation Subset:  IM; S    
Department of Physiology and Biophysics, Louisiana State University Medical Center, Shreveport 71130, USA.
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MeSH Terms
Anoxia / metabolism*,  pathology,  physiopathology
Cell Survival
Chronic Disease
Fructose / pharmacology
Glutathione / metabolism*
Ileum / metabolism,  pathology,  physiopathology
Jejunum / metabolism,  pathology,  physiopathology
Lactic Acid / pharmacology
Metabolic Detoxication, Drug
Oxidants / pharmacology
Oxygen Consumption
Peroxides / pharmacokinetics*
Proteins / metabolism
Rats, Sprague-Dawley
Sulfhydryl Compounds / metabolism
Grant Support
Reg. No./Substance:
0/Oxidants; 0/Peroxides; 0/Proteins; 0/Sulfhydryl Compounds; 30237-26-4/Fructose; 50-21-5/Lactic Acid; 70-18-8/Glutathione; 75-91-2/tert-Butylhydroperoxide

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