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PMID: 8617197 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Superoxide anion is a natural inhibitor of FAS-mediated cell death.

The EMBO journal ·Vol. 15 ·No. 2 ·1996-01-15 ·Pages 216-25

Clément MV, Stamenkovic I

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.

MeSH Terms
Antioxidants/pharmacology Apoptosis/drug effects Bone Neoplasms Cell Line Ditiocarb/pharmacology Enzyme Inhibitors/pharmacology Humans Kinetics Luminescent Measurements Melanoma Osteosarcoma Oxidative Stress Phorbol Esters/pharmacology Reactive Oxygen Species/pharmacology Recombinant Proteins/biosynthesis Superoxides/metabolism Transfection Tumor Cells, Cultured Tumor Necrosis Factor-alpha/biosynthesis,physiology Urinary Bladder Neoplasms fas Receptor/biosynthesis,physiology
Chemicals
Antioxidants Enzyme Inhibitors Phorbol Esters Reactive Oxygen Species Recombinant Proteins Tumor Necrosis Factor-alpha fas Receptor Superoxides Ditiocarb
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Clément M V
Department of Pathology, Harvard Medical School and Pathology Research, Boston, MA 02129, USA.
Stamenkovic I
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-01-15
Pages
216-25
Language
English
Region
England
NLM ID
8208664
PMCID
PMC449936
Subset
IM
Grants
NCI NIH HHS · CA55735 · United States
External Links
PubMed source PMC Full Text View journal details
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