Abstract
Hydrogen peroxide (H2O2) caused a rapid and a concentration-dependent increase in the activity of γ-glutamylcysteine synthetase (γ-GCS) in cultured Chinese hamster V79 cells. The increase in the activity was transient and declined rapidly during post-treatment incubation. Inhibition of protein synthesis by cycloheximide, chelation of divalent iron byo-phenanthroline, and scavenging of free radicals by butyl-4-hydroxyanisole failed to suppress the increase in activity of γ-GCS caused by H2O2. However, catalase completely inhibited the increase in the activity of the enzyme. H2O2 did not change the level of total glutathione (GSH+GSSG) but is oxidized GSH. The increased in levels of GSSG caused by H2O2 was enhanced byo-phenanthroline.
These results suggest that the increase in activity of γ-GCS caused by H2O2 is not an inducible phenomenon, nor it is attributable to the action of free radicals generated by an iron-catalyzed Fenton reaction. Furthermore, the changes in levels of GSH and GSSG caused by H2O2 appear not to be responsible for the increase in activity of γ-GCS caused by the hydroperoxide. However, chemical reduction of the enzyme, the activity of which had been increased by H2O2, resulted in a decrease, in the activity, suggesting the involvement of oxidation of the enzyme in the increased activity of γ-GCS caused by H2O2. The results also suggest that the activity of γ-GCS in cultured V79 cells can be regulated by the cellular oxidation-reduction state.
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Ochi, T. Hydrogen peroxide increases the activity of γ-glutamylcysteine synthetase in cultured Chinese hamster V79 cells. Arch Toxicol 70, 96–103 (1995). https://doi.org/10.1007/BF02733669
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DOI: https://doi.org/10.1007/BF02733669