Protective role of Bcl2 in metabolic oxidative stress-induced cell death

Previous studies have shown that overexpression of Bcl2 protects cells from glucose deprivation-induced cell death in multidrug-resistant human breast carcinoma, MCF-7/ADR cells, In this study, me further investigated the pro tective role of Bcl2 in glucose deprivation-induced cytotoxicity. Although Bcl2 did not prevent a 3,2-fold increase in the level of hydroperoxide duri ng glucose deprivation, it led to a compartmentalization of hydroperoxide m olecules in the mitochondria. It also inhibited glucose deprivation-induced cytochrome c release from the mitochondria. It is possible that overexpres sion of Bcl2 prevents glucose deprivation-induced ceramide generation, prob ably by preventing the leakage of hydroperoxide from the mitochondria. We a lso observed that glucose deprivation induced a sixfold increase in oxidize d glutathione content, as well as in thiol precursor content. Overexpressio n of Bcl2 suppressed an increase in oxidized glutathione content and thiol precursor content. Our results indicate that Bcl2 protects cells from metab olic oxidative stress-induced damage by inhibiting the leakage of hydropero xide from the mitochondria and subsequently preventing ceramide generation. Preventing ceramide generation inhibits the signal transduction pathway an d results in the suppression of cytochrome c release from the mitochondria.