Hydrogen peroxide increases the activity of gamma-glutamylcysteine synthetase in cultured Chinese hamster V79 cells. 1995

T Ochi
Department of Environmental Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.

Hydrogen peroxide (H2O2) caused a rapid and a concentration-dependent increase in the activity of gamma-glutamylcysteine synthetase (gamma-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 by o-phenanthroline, and scavenging of free radicals by butyl-4-hydroxyanisole failed to suppress the increase in activity of gamma-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 it oxidized GSH. The increase in levels of GSSG caused by H2O2 was enhanced by o-phenanthroline. These results suggest that the increase in activity of gamma-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 gamma-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 tha activity, suggesting the involvement of oxidation of the enzyme in the increased activity of gamma-GCS caused by H2O2. The results also suggest that the activity of gamma-GCS in cultured V79 cells can be regulated by the cellular oxidation-reduction state.

UI MeSH Term Description Entries
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008297 Male Males
D010084 Oxidation-Reduction A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). Redox,Oxidation Reduction
D010618 Phenanthrolines Phenanthroline
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D003412 Cricetulus A genus of the family Muridae consisting of eleven species. C. migratorius, the grey or Armenian hamster, and C. griseus, the Chinese hamster, are the two species used in biomedical research. Hamsters, Armenian,Hamsters, Chinese,Hamsters, Grey,Armenian Hamster,Armenian Hamsters,Chinese Hamster,Chinese Hamsters,Grey Hamster,Grey Hamsters,Hamster, Armenian,Hamster, Chinese,Hamster, Grey
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D005347 Fibroblasts Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. Fibroblast
D005721 Glutamate-Cysteine Ligase One of the enzymes active in the gamma-glutamyl cycle. It catalyzes the synthesis of gamma-glutamylcysteine from glutamate and cysteine in the presence of ATP with the formation of ADP and orthophosphate. EC 6.3.2.2. gamma-Glutamyl-Cysteine Synthetase,Glutamylcysteine Synthetase,Glutamate Cysteine Ligase,Ligase, Glutamate-Cysteine,Synthetase, Glutamylcysteine,Synthetase, gamma-Glutamyl-Cysteine,gamma Glutamyl Cysteine Synthetase
D005978 Glutathione A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides. Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine

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