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

FEBS Lett. 1998 Nov 27;440(1-2):13-8. doi: 10.1016/s0014-5793(98)01410-0.


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.

MeSH terms

  • Apoptosis*
  • Blotting, Western
  • Caspase Inhibitors
  • Caspases / metabolism
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Fluoresceins
  • Glutathione / metabolism*
  • Humans
  • Hydrogen Peroxide / pharmacology*
  • Hydrogen-Ion Concentration
  • Melanoma
  • NADH, NADPH Oxidoreductases / metabolism
  • Necrosis
  • Oxidation-Reduction
  • Poly(ADP-ribose) Polymerases / metabolism
  • RNA, Antisense / genetics
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Superoxides / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transfection
  • Tumor Cells, Cultured


  • Caspase Inhibitors
  • Fluoresceins
  • RNA, Antisense
  • Superoxides
  • 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein
  • Hydrogen Peroxide
  • Superoxide Dismutase
  • NADH, NADPH Oxidoreductases
  • Poly(ADP-ribose) Polymerases
  • Caspases
  • Glutathione
  • Tetradecanoylphorbol Acetate