Apoptosis induced by hydrogen peroxide is mediated by decreased superoxide anion concentration and reduction of intracellular milieu

Hydrogen peroxide (H2O2) is considered to be a mediator of apoptotic cell death but the mechanism by which it induces apoptosis is unclear, Here, me show that cells undergoing apoptosis from exposure to H2O2 display a significant decrease in intracellular concentration of superoxide (O-2(-)) which is associated with a reduction of the intracellular milieu, as measured by an increase in the GSH/GSSG ratio and a decrease in intracellular pH, The notion that a decrease in intracellular O-2(-) concentration triggers apoptosis is supported by the observation that H2O2-mediated apoptosis could be retarded in cells in which the intracellular O-2(-) concentration is maintained at or above the cellular baseline level by inhibition of the major O-2(-) scavenger superoxide dismutase (Cu/Zn SOD), Taken together, our observations indicate that a decrease in the intracellular O-2(-) concentration, reduction and acidification of the intracellular milieu constitute a signal for H2O2-mediated apoptosis, thereby inducing a reductive as opposed to an oxidative stress. (C) 1998 Federation of European Biochemical Societies.