Induction of apoptosis and of interleukin-1beta secretion by 7beta-hydroxycholesterol and 7-ketocholesterol: partial inhibition by Bcl-2 overexpression.
The oxysterols, 7beta-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. 7Beta-hydroxycholesterol and 7-ketocholesterol induced nuclear condensation and/or fragmentation, internucleosomal DNA fragmentation, and IL-1beta 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-1beta release which might favor the recruitment of immunocompetent cells in the atherosclerotic plaque.
Lizard
G
G
Laboratoire de Biochimie des Lipoprotéines, INSERM CJF 93-10, Faculté de Médecine, Dijon, France.
Lemaire
S
S
Monier
S
S
Gueldry
S
S
Néel
D
D
Gambert
P
P
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology*; D007375:Interleukin-1 / Q000378:metabolism*; D007653:Ketocholesterols / Q000494:pharmacology*; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D014407:Tumor Cells, Cultured
D006888:Hydroxycholesterols; D007375:Interleukin-1; D007653:Ketocholesterols; D019253:Proto-Oncogene Proteins c-bcl-2; C011724:cholest-5-en-3 beta,7 alpha-diol; C003001:7-ketocholesterol