Yang Jun-Yao, Hu Yan-Wei, Zhang Peng, Zheng Lei, Wang Qian
Laboratory Medicine Centre, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Sheng Li Xue Bao. 2012 Dec 25;64(6):721-8.
The polytopic transmembrane protein, Niemann-Pick type C1 Like 1 (NPC1L1), is the key point of exogenous cholesterol absorption and plays an important role in cholesterol metabolism. However, the molecular mechanism of NPC1L1's role in cholesterol uptake remains unclear. NPC1L1 expression is highly regulated by a variety of molecular actors. Nuclear receptors regulate NPC1L1 expression through its promoter region. Polyunsaturated fatty acids down-regulates NPC1L1 expression by the way of sterol regulatory element binding protein 2 (SREBP2). In addition, curcumin and sphingosine-phosphate take part in the regulation of NPC1L1 expression. NPC1L1 has been recognized as an essential protein for sterol absorption and is the molecular target of ezetimibe. Moreover, inhibition of the expression of NPC1L1 has been shown to have beneficial effects on components of the metabolic syndrome. The recent progress in the structure, function and regulation of NPC1L1 is reviewed.
多聚跨膜蛋白尼曼-匹克C1样蛋白1(NPC1L1)是外源性胆固醇吸收的关键,在胆固醇代谢中起重要作用。然而,NPC1L1在胆固醇摄取中作用的分子机制仍不清楚。NPC1L1的表达受到多种分子因素的高度调控。核受体通过其启动子区域调节NPC1L1的表达。多不饱和脂肪酸通过固醇调节元件结合蛋白2(SREBP2)下调NPC1L1的表达。此外,姜黄素和鞘氨醇-1-磷酸参与NPC1L1表达的调节。NPC1L1已被认为是固醇吸收的必需蛋白,是依泽替米贝的分子靶点。此外,抑制NPC1L1的表达已显示对代谢综合征的组分具有有益作用。本文综述了NPC1L1在结构、功能和调节方面的最新进展。