Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
Department of Electrocardiogram, the Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
Clin Chim Acta. 2014 Feb 15;429:69-75. doi: 10.1016/j.cca.2013.11.026. Epub 2013 Dec 1.
Post-lysosomal cholesterol trafficking is an important, but poorly understood process that is essential to maintain lipid homeostasis. Niemann-Pick type C1 (NPC1), an integral membrane protein on the limiting membrane of late endosome/lysosome (LE/LY), is known to accept cholesterol from NPC2 and then mediate cholesterol transport from LE/LY to endoplasmic reticulum (ER) and plasma membrane in a vesicle- or oxysterol-binding protein (OSBP)-related protein 5 (ORP5)-dependent manner. Mutations in the NPC1 gene can be found in the majority of NPC patients, who accumulate massive amounts of cholesterol and other lipids in the LE/LY due to a defect in intracellular lipid trafficking. Liver X receptor (LXR) is the major positive regulator of NPC1 expression. Atherosclerosis is the pathological basis of coronary heart disease, one of the major causes of death worldwide. NPC1 has been shown to play a critical role in the atherosclerotic progression. In this review, we have summarized the role of NPC1 in regulating intracellular cholesterol trafficking and atherosclerosis.
溶酶体后胆固醇转运是一个重要但尚未充分了解的过程，对于维持脂质稳态至关重要。尼曼-匹克 C1 型（NPC1）是晚期内体/溶酶体（LE/LY）限制膜上的一种完整膜蛋白，已知它从 NPC2 接受胆固醇，然后以囊泡或氧化固醇结合蛋白（OSBP）相关蛋白 5（ORP5）依赖的方式将胆固醇从 LE/LY 转运到内质网（ER）和质膜。NPC 患者的大多数都存在 NPC1 基因的突变，由于细胞内脂质转运的缺陷，这些患者的 LE/LY 中会积累大量的胆固醇和其他脂质。肝 X 受体（LXR）是 NPC1 表达的主要正向调节因子。动脉粥样硬化是冠心病的病理基础，也是全球主要死亡原因之一。NPC1 已被证明在动脉粥样硬化的进展中起着关键作用。在这篇综述中，我们总结了 NPC1 在调节细胞内胆固醇转运和动脉粥样硬化中的作用。
