Thiol Oxidation Enforces Phosphatidylserine Externalization in Apoptosis-Sensitive and -Resistant Cells Through a Δψm/Cytochrome c Release-Dependent Mechanism

A. Johanna Forsberg, Valerian E. Kagan, Alan J. Schroit

Research output: Contribution to journalReview article

10 Scopus citations


Previous studies have shown that unlike most apoptotic cells, Raji cells do not externalize phosphatidylserine (PS) upon apoptosis. Here we show that Raji cells are resistant to intrinsic apoptogenic agents, but sensitive to extrinsically triggered Fas-induced apoptosis. Treatment of intrinsic apoptosis-competent Jurkat cells with vitamin E implicated reactive oxygen species in intrinsic apoptosis because, like Raji cells, they became resistant to actinomycin D- but not Fas-triggered apoptosis. Oxidation of sulfhydryls in both cell types with N-ethylmaleimide resulted in rapid disruption of the mitochondrial membrane potential, release of cytochrome c from the mitochondria to the cytoplasm, and externalization of PS by a mechanism that was not inhibited by the pan caspase inhibiter zVAD-fmk. These results suggest that although cell death and PS externalization are both cytochrome c-dependent, they are distinct and separable processes.

Original languageEnglish (US)
Pages (from-to)203-208
Number of pages6
JournalAntioxidants and Redox Signaling
Issue number2
StatePublished - Apr 1 2004


ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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