4-Hydroxynonenal Induces Apoptosis via Caspase-3 Activation and Cytochrome c Release

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• 作者：Chuan Ji ; Ventkataraman Amarnath ; Jennifer A. Pietenpol ; and Lawrence J. Marnett
• 刊名：Chemical Research in Toxicology
• 出版年：2001
• 出版时间：August 2001
• 年：2001
• 卷：14
• 期：8
• 页码：1090 - 1096
• 全文大小：195K
• 年卷期：v.14,no.8(August 2001)
• ISSN：1520-5010

文摘

We investigated the mechanism by which 4-hydroxynonenal (HNE), a major aldehydic productof lipid peroxidation, induces apoptosis in tumor cells. Treatment of human colorectal carcinoma(RKO) cells with HNE-induced poly-ADP-ribose-polymerase (PARP) cleavage and DNAfragmentation in a dose- and time-dependent manner. The induction of PARP cleavage andDNA fragmentation paralleled caspase-2, -3, -8, and -9 activation. Pretreatment of cells withan inhibitor of caspase-3, z-DEVD-fmk, or a broad spectrum caspase inhibitor, z-VAD-fmk,abolished caspase activation and subsequent PARP cleavage. Constitutive expression of highlevels of Bcl-2 protected cells from HNE-mediated apoptosis. In addition, Bcl-2 overexpressioninhibited cytochrome c release from mitochondria and subsequent caspase-2, -3, and -9activation. These findings demonstrate that HNE triggers apoptotic cell death through amitochondrion-dependent pathway involving cytochrome c release and caspase activation. Bcl-2overexpression protected cells from HNE-induced apoptosis through inhibition of cytochromec release.