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, we show that cells undergoing apoptosis from exposure to H2O2 display a significant decrease in intracellular concentration of superoxide (O2-) 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 O2- concentration triggers apoptosis is supported by the observation that H2O2-mediated apoptosis could be retarded in cells in which the intracellular O2- concentration is maintained at or above the cellular baseline level by inhibition of the major O2- scavenger superoxide dismutase (Cu/Zn SOD). Taken together, our observations indicate that a decrease in the intracellular O2- 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.
Clément
M V
MV
Oncology Research Institute, National University Medical Institutes, Clinical Research Centre, Singapore, Singapore. nmimvc@leonis.nus.edu.sg
Ponton
A
A
Pervaiz
S
S
D017209:Apoptosis; D015153:Blotting, Western; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005452:Fluoresceins; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D008545:Melanoma; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism; D009336:Necrosis; D010084:Oxidation-Reduction; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D016372:RNA, Antisense / Q000235:genetics; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D061945:Caspase Inhibitors; D005452:Fluoresceins; D016372:RNA, Antisense; D013481:Superoxides; C043829:2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D005978:Glutathione; D013755:Tetradecanoylphorbol Acetate