THE ROLE OF INTRACELLULAR OXIDANTS IN APOPTOSIS

Apoptotic cell death is a complex process whose biochemistry is poorly understood. Direct exposure of various cell types to oxidants such as hydrogen peroxide or lipid hydroperoxides can directly induce apoptos is, while in many experimental models pretreatment of cells with antio xidants has been shown to protect against this form of cell death. Rec ent experimental evidence suggests that multiple forms of thymocyte ap optosis can be inhibited by free radical spin traps, spin probes and t hiol reductants, and that this inhibition correlates with a lower oxid ative burden within the treated cells. Possible sites of production of these oxidants include mitochondrial electron transport and phospholi pase A(2)-activated arachidonic acid metabolism, while intracellular t argets may include redox sensitive transcription factors and inhibitor y proteins that must be tagged for proteolysis before apoptosis can co mmence.