Development Research, Pharmaceutical Research Center, Mochida Pharmaceutical Co., Ltd., Shizuoka 412-8524, Japan.
Prostaglandins Leukot Essent Fatty Acids. 2010 Aug;83(2):75-81. doi: 10.1016/j.plefa.2010.05.002. Epub 2010 Jun 12.
Cide-a and Cide-c belong to the cell death-inducing DNA fragmentation factor-alpha-like effector family. Recent evidences suggest that these proteins may be involved in lipid accumulation in liver and adipose tissues. We confirmed that in the high-fat/high-sucrose diet-induced murine model of hepatic steatosis, the expression levels of the Cide-a and Cide-c genes were markedly and time-dependently increased, but returned to normal levels following improvement of hepatic steatosis by eicosapentaenoic acid (EPA) administration. Levels of expression of the Cide-a and Cide-c genes correlated well with plasma ALT. EPA inhibited the promoter activity of the Cide-a gene in vitro. Sterol regulatory element-binding protein-1 (SREBP-1) markedly enhanced the promoter activity of Cide-a, and EPA inhibited the expression of Cide-a mRNA. SREBP-1 and EPA did not affect those of Cide-c. These findings indicate that Cide-a and Cide-c are closely involved in the progression of hepatic steatosis, and that EPA inhibits Cide-a gene expression through SREBP-1 regulation.
Cide-a 和 Cide-c 属于细胞死亡诱导 DNA 片段化因子-α样效应因子家族。最近的证据表明，这些蛋白质可能参与肝脏和脂肪组织中的脂质积累。我们证实，在高脂肪/高蔗糖饮食诱导的肝脂肪变性小鼠模型中，Cide-a 和 Cide-c 基因的表达水平显著且时间依赖性增加，但在用二十碳五烯酸 (EPA) 治疗改善肝脂肪变性后恢复正常水平。Cide-a 和 Cide-c 基因的表达水平与血浆 ALT 密切相关。EPA 在体外抑制 Cide-a 基因的启动子活性。固醇调节元件结合蛋白-1 (SREBP-1) 显著增强 Cide-a 的启动子活性，而 EPA 抑制 Cide-a mRNA 的表达。SREBP-1 和 EPA 不影响 Cide-c 的表达。这些发现表明 Cide-a 和 Cide-c 密切参与肝脂肪变性的进展，而 EPA 通过 SREBP-1 调节抑制 Cide-a 基因表达。
Zotero 插件