Turning point in apoptosis/necrosis induced by hydrogen peroxide

Yoshiro Saito, Keiko Nishio, Yoko Ogawa, Junko Kimata, Tomoya Kinumi, Yasukazu Yoshida, Noriko Noguchi, Etsuo Niki

Research output: Contribution to journalArticlepeer-review

119 Citations (Scopus)

Abstract

The turning point between apoptosis and necrosis induced by hydrogen peroxide (H2O2) have been investigated using human T-lymphoma Jurkat cells. Cells treated with 50 μM H2 O2 exhibited caspase-9 and caspase-3 activation, finally leading to apoptotic cell death. Treatment with 500 μM H2 O2 did not exhibit caspase activation and changed the mode of death to necrosis. On the other hand, the release of cytochrome c from the mitochondria was observed under both conditions. Treatment with 500 μM H2O2, but not with 50 μM H2 O2, caused a marked decrease in the intracellular ATP level; this is essential for apoptosome formation. H2O2 -reducing enzymes such as cellular glutathione peroxidase (cGPx) and catalase, which are important for the activation of caspases, were active under the 500 μM H2O2 condition. Prevention of intracellular ATP loss, which did not influence cytochrome c release, significantly activated caspases, changing the mode of cell death from necrosis to apoptosis. These results suggest that ATP-dependent apoptosome formation determines whether H2 O2-induced cell death is due to apoptosis or necrosis.

Original languageEnglish
Pages (from-to)619-630
Number of pages12
JournalFree Radical Research
Volume40
Issue number6
DOIs
Publication statusPublished - 2006 Jun 1
Externally publishedYes

Keywords

  • ATP
  • Apoptosis
  • Apoptosome
  • Hydrogen peroxide
  • Necrosis
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry

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