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Induction of apoptosis and of interleukin-1β secretion by 7β-hydroxycholesterol and 7-ketocholesterol: partial inhibition by Bcl-2 overexpression

The oxysterols, 7β-hydroxycholesterol and 7-ketocholesterol, are involved in the cytotoxicity of oxidized LDL. To elucidate their molecular mechanisms, the human promonocytic leukemia cells U937 and U4 were used. U4 cells overexpressing Bcl-2 were obtained by transfection of U937 cells. 7β-hydroxych...

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Published in:FEBS letters 1997-12, Vol.419 (2), p.276-280
Main Authors: Lizard, Gérard, Lemaire, Stéphanie, Monier, Serge, Gueldry, Serge, Néel, Dominique, Gambert, Philippe
Format: Article
Language:English
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Summary:The oxysterols, 7β-hydroxycholesterol and 7-ketocholesterol, are involved in the cytotoxicity of oxidized LDL. To elucidate their molecular mechanisms, the human promonocytic leukemia cells U937 and U4 were used. U4 cells overexpressing Bcl-2 were obtained by transfection of U937 cells. 7β-hydroxycholesterol and 7-ketocholesterol induced nuclear condensation and/or fragmentation, internucleosomal DNA fragmentation, and IL-1β secretion, which were partially inhibited by Bcl-2 overexpression. These findings underline that these oxysterols could constitute major risk factors in atherosclerosis by their cytotoxicity and their ability to induce IL-1β release which might favor the recruitment of immunocompetent cells in the atherosclerotic plaque.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(97)01473-7