Superoxide anion is a natural inhibitor of Fas-mediated cell death

Marie Véronique Clément, Ivan Stamenkovic

Research output: Contribution to journalArticlepeer-review

235 Scopus citations

Abstract

The cell surface receptor Fas is a major trigger of apoptosis. However, expression of the Fas receptor in many tumor cell types does not correlate with sensitivity to Fas-mediated cell death. Because a prooxidant state is a common feature of tumor cells, we examined the role of intracellular reactive oxygen intermediates in the regulation of Fas-mediated cytotoxicity. Our results show that an oxidative stress induced by increasing the intracellular superoxide anion (O2-) concentration can abrogate Fas-mediated apoptosis in cells which are constitutively sensitive to Fas. Conversely, an O2- concentration decrease is observed to sensitize cells which are naturally resistant to Fas signals. These observations suggest that intracellular O2- may play a key role in regulating cell sensitivity to a potentially lethal signal and provide tumor cells with a natural, inducible mechanism of resistance to Fas-mediated apoptosis.

Original languageEnglish
Pages (from-to)216-225
Number of pages10
JournalEMBO Journal
Volume15
Issue number2
DOIs
StatePublished - 15 Jan 1996
Externally publishedYes

Keywords

  • Apoptosis
  • Fas
  • Superoxide anion
  • Tumor cells

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