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Superoxide anion is a natural inhibitor of FAS‐mediated cell death.
Author(s) -
Clément M. V.,
Stamenkovic I.
Publication year - 1996
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1996.tb00352.x
Subject(s) - intracellular , superoxide , apoptosis , biology , programmed cell death , microbiology and biotechnology , fas receptor , reactive oxygen species , cell , cytotoxicity , receptor , fas ligand , biochemistry , in vitro , enzyme
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.