Effect of exogenous and endogenous nitric oxide on mitochondrial respiration of rat hepatocytes
American Journal of Physiology-Cell PhysiologyPublished 1 May 1991
J. Stadler, Timothy R. Billiar, Ronald Curran, Dennis J. Stuehr, Juan B. Ochoa, Richard L. Simmons
Citations400
SJR quartileQ1
SJR score1.79
SNIP1.26
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TL;DR
Endogenous .N = O biosynthesis was induced in HC by a specific combination of cytokines and lipopolysaccharide, and a concentration-dependent inhibition of mitochondrial aconitase, NADH-ubiquinone oxidoreductase, and succinate-ubsinone oxidation chain was observed.
Abstract
Although nitric oxide (.N = O) biosynthesis is inducible in rat hepatocytes (HC), the physiological significance of .N = O production by these cells is unknown. Short exposure of HC to authentic .N = O led to a concentration-dependent inhibition of mitochondrial aconitase, NADH-ubiquinone oxidoreductase, and succinate-ubiquinone oxidoreductase (complexes I and II of the mitochondrial electron transport chain). Most susceptible to .N = O inhibition was mitochondrial aconitase, in which a reduction in enzyme activity to 20.2 +/- 1.6% of control was observed. In contrast to mitochondrial aconitase, cytosolic aconitase activity was not inhibited by .N = O. After exposure to a maximal inhibitory concentration of .N = O, mitochondrial aconitase activity recovered completely within 6 h. Complex I did not fully recover within this incubation period. Endogenous .N = O biosynthesis was induced in HC by a specific combination of cytokines and lipopolysaccharide. After 18 h of incubation with these stimuli, a significant inhibition of mitochondrial aconitase activity to 70.8 +/- 2.4% of controls was detected. However, this was due only in part to the action of .N = O. A non- .N = O-dependent inhibition of mitochondrial function appeared to be mediated by tumor necrosis factor.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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