Ory Daniel S
Daniel S. Ory is at the Center for Cardiovascular Research, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Trends Cardiovasc Med. 2004 Feb;14(2):66-72. doi: 10.1016/j.tcm.2003.12.003.
Cellular cholesterol homeostasis is maintained through activation of the designated sterol regulatory element binding proteins and liver X receptor transcriptional pathways. Insight into the molecular mechanisms that regulate these pathways has come from the study of Niemann-Pick C (NPC) disease. Mutations in the NPC1 and NPC2 disease genes lead to lysosomal accumulation of cholesterol and defects in regulation of sterol homeostatic responses. NPC1 and NPC2 are key participants in intracellular cholesterol trafficking and are required for production of low-density lipoprotein cholesterol-derived oxysterols. In this review, the function of NPC1 and NPC2 in sterol trafficking and regulation of cholesterol homeostasis is examined. Study of the NPC proteins will further understanding of the mechanisms involved in atherogenesis.
细胞胆固醇稳态通过特定的固醇调节元件结合蛋白和肝脏X受体转录途径的激活得以维持。对调节这些途径的分子机制的深入了解来自于尼曼-皮克C型（NPC）病的研究。NPC1和NPC2疾病基因的突变导致胆固醇在溶酶体中积累，并在固醇稳态反应调节方面出现缺陷。NPC1和NPC2是细胞内胆固醇转运的关键参与者，也是产生低密度脂蛋白胆固醇衍生的氧化固醇所必需的。在这篇综述中，研究了NPC1和NPC2在固醇转运和胆固醇稳态调节中的功能。对NPC蛋白的研究将进一步加深对动脉粥样硬化发生机制的理解。
