Activation of rat liver microsomal glutathione S-transferase by reduced oxygen species.
The effect of enzymatically generated reduced oxygen metabolites on the activity of hepatic microsomal glutathione S-transferase activity was studied to explore possible physiological regulatory mechanisms of the enzyme. Noradrenaline and the microsomal cytochrome P-450-dependent monooxygenase system were used to generate reduced oxygen species. When noradrenaline (greater than 0.1 mM) was incubated with rat liver microsomes in phosphate buffer (pH 7.4), an increase in microsomal glutathione S-transferase activity was observed, and this activation was potentiated in the presence of a NADPH-generating system; the glutathione S-transferase activity was increased to 180% of the control with 1 mM noradrenaline and to 400% with both noradrenaline and NADPH. Superoxide dismutase and catalase inhibited partially the noradrenaline-dependent activation of the enzyme. In the presence of dithiothreitol and glutathione, the activation of the glutathione S-transferase by noradrenaline, with or without NADPH, was not observed. In addition, the activation of glutathione S-transferase activity by noradrenaline and glutathione disulfide was not additive when both compounds were incubated together. These results indicate that the microsomal glutathione S-transferase is activated by reduced oxygen species, such as superoxide anion and hydrogen peroxide. Thus, metabolic processes that generate high concentrations of reduced oxygen species may activate the microsomal glutathione S-transferase, presumably by the oxidation of the sulfhydryl group of the enzyme, and this increased catalytic activity may help protect cells from oxidant-induced damage.
Aniya
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Laboratory of Physiology and Pharmacology, School of Health Sciences, University of Ryukyus, Okinawa, Japan.
Anders
M W
MW
D000818:Animals; D002374:Catalase / Q000494:pharmacology*; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology*; D005978:Glutathione / Q000031:analogs & derivatives / Q000494:pharmacology; D019803:Glutathione Disulfide; D005982:Glutathione Transferase / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008862:Microsomes, Liver / Q000201:enzymology*; D009638:Norepinephrine / Q000494:pharmacology*; D010084:Oxidation-Reduction; D051381:Rats; D013482:Superoxide Dismutase / Q000494:pharmacology*
D008353:Mannitol; D002374:Catalase; D013482:Superoxide Dismutase; D005982:Glutathione Transferase; D005978:Glutathione; D004229:Dithiothreitol; D019803:Glutathione Disulfide; D009638:Norepinephrine; D004837:Epinephrine