Inhibition of the activity of glutathione peroxidase by tertiary-butylhydroperoxide in cultured Chinese hamster cells and the role of cellular glutathione in the recovery of the activity.
Treatment of Chinese hamster cells with 1 mM tertiary-butylhydroperoxide (t-BuOOH) for 1 h markedly inhibited the activity of glutathione peroxidase (GSH-Px). However, the activity returned to pre-inhibition levels within 1-2 h with post-treatment incubation. The inhibition of the activity of GSH-Px by t-BuOOH was enhanced by depletion of levels of cellular GSH with the addition of L-buthionine sulfoximine (BSO) or diethylmaleate (DEM) and no subsequent recovery of the activity was observed for at least 4 h. The ratio of levels of GSSG to total GSH increased as a result of treatment with 1 mM t-BuOOH or diamide for 1 h but not as a result of treatment with hydrogen peroxide. After treatment with t-BuOOH, the level of GSH rapidly increased to more than twice the control level during 15-40 min of post-treatment incubation. Depletion of GSH by DEM after treatment with t-BuOOH reduced the rate of the recovery of the activity of GSH-Px, suggesting a role of cellular GSH in the recovery. However, the decrease in the rate of the recovery caused by DEM was small and in no way equivalent to the extent of depletion of GSH, suggesting that the rapid increase in the level of GSH after treatment with t-BuOOH is not closely related to the rapid recovery of the activity of GSH-Px.
Ochi
T
T
Department of Environmental Toxicology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa, Japan.
D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004347:Drug Interactions; D005978:Glutathione / Q000502:physiology*; D005979:Glutathione Peroxidase / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010545:Peroxides / Q000494:pharmacology*; D020122:tert-Butylhydroperoxide
D000963:Antimetabolites; D010545:Peroxides; D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D020122:tert-Butylhydroperoxide; D005979:Glutathione Peroxidase; D005978:Glutathione