Document Detail

Inhibition of cytochrome-c oxidase activity during prolonged hypoxia.
MedLine Citation:
PMID:  7611433     Owner:  NLM     Status:  MEDLINE    
During acute (< 30 min) hypoxia, cellular respiration is independent of the O2 concentration as long as PO2 remains above a critical value (5-10 Torr). Similarly, state 3 respiration by isolated mitochondria is independent of PO2 above a critical tension of 2-4 Torr. However, rat hepatocytes demonstrate a reversible suppression of respiration and an increase in NAD(P)H concentration during prolonged (2-24 h), but not acute hypoxia [P. T. Schumacker, N. Chandel, and A. G. N. Augusti. Am. J. Physiol. 265 (Lung Cell. Mol. Physiol. 9): L395-L402, 1993]. This study tested whether respiration is similarly inhibited in isolated mitochondria exposed to low PO2 for prolonged periods and whether cytochrome-c oxidase participates in this response. Coupled rat liver mitochondria were incubated under low oxygen conditions (PO2 < 2 Torr) for 2 h. State 3 respiration after reoxygenation to PO2 = 20 Torr was then compared with the value obtained subsequently at 100 Torr. Using succinate and ADP as substrates, we determined that state 3 respiration at 20 Torr was 61.0 +/- 8.4% of the subsequent value at 100 Torr (P < 0.05). By contrast, control mitochondria reoxygenated to 100 Torr first and 20 Torr subsequently showed no significant difference at the two O2 tensions (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
N Chandel; G R Budinger; R A Kemp; P T Schumacker
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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:  268     ISSN:  0002-9513     ISO Abbreviation:  Am. J. Physiol.     Publication Date:  1995 Jun 
Date Detail:
Created Date:  1995-08-15     Completed Date:  1995-08-15     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:  L918-25     Citation Subset:  IM    
Department of Medicine, University of Chicago, Illinois 60637, USA.
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MeSH Terms
Calcimycin / pharmacology
Cell Hypoxia
Electron Transport Complex IV / antagonists & inhibitors*
Mitochondria, Liver / enzymology*,  metabolism
Oxidative Phosphorylation
Oxygen / pharmacology
Oxygen Consumption / drug effects
Partial Pressure
Rats, Sprague-Dawley
Grant Support
Reg. No./Substance:
52665-69-7/Calcimycin; 7782-44-7/Oxygen; EC Transport Complex IV

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