Bcl‐2 protein inhibits oxysterol‐induced apoptosis through suppressing CPP32‐mediated pathway

FEBS Letters

Yagyu, Hiroaki¹  Yazaki, Yoshio¹  Harada, Kenji¹  Ohashi, Ken¹  Miyashita, Toshiyuki²  Ishibashi, Shun¹  Osuga, Jun-ichi¹  Yamada, Nobuhiro¹ 

[1] Third Department of Internal Medicine, University of Tokyo, Tokyo, Japan;Department of Genetics, National Children's Medical Research Center, Tokyo, Japan

关键词: Oxysterol;    Apoptosis;    Cytotoxicity;    Bcl-2;    LDL;    low density lipoprotein;    HMG-CoA;    3-hydroxy-3-methylglutalyl coenzyme A;    ICE;    interleukin-1β converting enzyme;    Ac-DEVD-CHO;    acetyl-Asp-Glu-Val-Asp-CHO;   

DOI  :  10.1016/S0014-5793(97)00662-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Oxysterols are presumed to mediate cytotoxicity of oxidized LDL in atherosclerotic lesions. To elucidate its molecular mechanism, we established murine macrophage-like P388-D1 cells which over-express Bcl-2 protein by retrovirus-mediated gene transfer. Oxysterols (7-ketocholesterol, 25-hydroxycholesterol) induced nuclear condensation and oligonucleosomal DNA fragmentation, which were partially inhibited by Bcl-2 over-expression. Though CPP32 inhibitor suppressed the cell death in control cells, it showed no additive protection in the cells over-expressing Bcl-2. These findings indicate that oxysterols induce apoptosis via Bcl-2-inhibitable and -uninhibitable pathways, and the former depends on CPP32 activation.

【 授权许可】

Unknown