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Bcl‐2 protein inhibits oxysterol‐induced apoptosis through suppressing CPP32‐mediated pathway
Author(s) -
Harada Kenji,
Ishibashi Shun,
Miyashita Toshiyuki,
Osuga Jun-ichi,
Yagyu Hiroaki,
Ohashi Ken,
Yazaki Yoshio,
Yamada Nobuhiro
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00662-5
Subject(s) - oxysterol , apoptosis , dna fragmentation , cytotoxicity , microbiology and biotechnology , chemistry , fragmentation (computing) , programmed cell death , transfection , biochemistry , biology , gene , in vitro , cholesterol , ecology
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.
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