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J. L. Goldstein, M. S. Brown. Regulation of the mevalonate pathway. Nature, 1990, 343(6257): 425-430.

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  • 标题: 胆固醇吸收靶点NPC1L1研究进展Research Progress of Niemann-Pick-C1-Like 1, a Key Target Related to Cholesterol Absorption

    作者: 方沐潮, 曹乐, 贝伟剑

    关键字: 胆固醇吸收, NPC1L1, 中药, 依泽麦布Cholesterol Absorption; Niemann-Pick-C1-Like 1; Traditional Chinese Medicine; Ezetimibe

    期刊名称: 《Pharmacy Information》, Vol.2 No.2, 2013-05-28

    摘要: NPC1L1是近年发现对胆固醇的吸收有调控作用的新靶点。在小肠内NPC1L1蛋白与胆固醇吸收直接相关。NPC1L1蛋白与相关胆固醇转运蛋白Flotillin-1和Flotillin-2相互作用,将胆固醇和其他甾醇转运通过肠上皮细胞刷状缘、运送到肠上皮细胞内。降胆固醇药物Ezetimibe正是阻断了NPC1L1和Flotillin-1和Flotillin-2的相互作用,从而抑制胆固醇吸收。NPC1L1的表达受到多个核因子如PPARs,LXRα,SREBP2,HNF4α的调控;另一方面,NPC1L1又能够通过调节细胞胆固醇水平,进而调控胆固醇代谢相关的SREBP1c、FAS和ABCA1等基因,进一步维持体内胆固醇的动态平衡。多种中药对胆固醇吸收有抑制作用,但是目前尚未发现中药直接作用于NPC1L1而抑制胆固醇吸收的报道。NPC1L1 is a new found target protein in the regulation of cholesterol absorption. NPC1L1 is directly related to cholesterol absorption in the intestine. By interacting with cholesterol transport protein Flotillin-1 and Flotillin-2, NPC1L1 protein transports the cholesterol and other sterols across the intestinal epithelial brush border membrane into the intestinal epithelial cells. The cholesterol transporter function of NPC1L1 was specifically inhibited by cholesterol- lowering agent Ezetimibe via blocking the interaction. NPC1L1 expression is highly modulated by a variety of nuclear regulators such as PPARs, LXRα, SREBP2, HNF4α. NPC1L1 could otherwise regulate the related downstream genes to maintain cholesterol homeostasis via regulating cholesterol level in the related cells. A variety of traditional Chinese medicine have inhibitory effect on cholesterol absorption. It has not yet reported that Traditional Chinese Medicine could regulate cholesterol absorption by inhibiting NPC1L1.

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