Abstract
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.
MeSH terms
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Animals
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Apoptosis*
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Caspase 3
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Caspases*
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Cell Line
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Cysteine Endopeptidases / metabolism*
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Cysteine Proteinase Inhibitors / pharmacology
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Hydroxycholesterols / antagonists & inhibitors
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Hydroxycholesterols / pharmacology*
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Ketocholesterols / antagonists & inhibitors
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Ketocholesterols / pharmacology*
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Macrophages / cytology
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Macrophages / drug effects
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Mice
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Oligopeptides / pharmacology
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Proto-Oncogene Proteins c-bcl-2 / genetics
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Proto-Oncogene Proteins c-bcl-2 / metabolism*
Substances
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Cysteine Proteinase Inhibitors
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Hydroxycholesterols
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Ketocholesterols
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Oligopeptides
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Proto-Oncogene Proteins c-bcl-2
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acetyl-aspartyl-glutamyl-valyl-aspartal
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25-hydroxycholesterol
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Casp3 protein, mouse
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Caspase 3
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Caspases
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Cysteine Endopeptidases
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7-ketocholesterol