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标题：Apoptosis induced by t10,c12-conjugated linoleic acid is mediated by an atypical endoplasmic reticulum stress response
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作者：Lihui Ou ; Yue Wu ; Clement Ip 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2008
卷号：49
期号：5
页码：985-994
DOI：10.1194/jlr.M700465-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Conjugated linoleic acid (CLA) inhibits rat mammary carcinogenesis, in part by inducing apoptosis of preneoplastic and neoplastic mammary epithelial cells. The current study focused on the mechanism by which apoptosis is induced. In TM4t mammary tumor cells, trans -10, cis -12 (t10,c12)-CLA induced proapoptotic C/EBP-homologous protein (CHOP) concurrent with the cleavage of poly(ADP-ribose) polymerase. Knockdown of CHOP attenuated t10,c12-CLA-induced apoptosis. Furthermore, t10,c12-CLA induced the cleavage of endoplasmic reticulum (ER)-resident caspase-12, and a selective inhibitor of caspase-12 significantly alleviated t10,c12-CLA-induced apoptosis. Using electron microscopy, we observed that t10,c12-CLA treatment resulted in marked dilatation of the ER lumen. Together, these data suggest that t10,c12-CLA induces apoptosis through ER stress. To further explore the ER stress pathway, we examined the expression of the following upstream ER stress signature markers in response to CLA treatment: X-box binding protein 1 (XBP1) mRNA (unspliced and spliced), phospho-eukaryotic initiation factor (eIF) 2α, activating transcription factor 4 (ATF4), and BiP proteins. We found that t10,c12-CLA induced the expression and splicing of XBP1 mRNA as well as the phosphorylation of eIF2α. In contrast, ATF4 was induced modestly, but not significantly, and BiP was not altered. In summary, our data demonstrate that apoptosis induced by t10,c12-CLA is mediated, at least in part, through an atypical ER stress response that culminates in the induction of CHOP and the cleavage of caspase-12.