C型尼曼-匹克蛋白1和2在细胞内脂质平衡中的作用  

Roles of NPC1 and NPC2 in intracellular lipid homeostasis

作　　者：欧翔[1] 唐朝克[1] 

机构地区：[1]南华大学心血管病研究所,湖南衡阳421001

出　　处：《中国病理生理杂志》2007年第4期820-824,共5页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.30470720);湖南省自然科学基金资助项目(No.06jj5058)

摘　　要：Niemann-pick protein C1(NPC1) is a large integral membrane glycoprotein that resides in late endosomes,whereas niemann-pick protein C2(NPC2) is a small soluble protein found in the lumen of lysosomes.NPC1 protein is believed to facilitate the transport of lipids,particularly cholesterol,from late endosomes/lysosomes to the Golgi apparatus,endoplasmic reticulum and plasma membrane.NPC2 primarily plays a role in the egress of cholesterol and glycolipids from lysosomes.Mutations in either NPC1 or NPC2 result in aberrant lipid transport from endocytic compartments,which results in lysosomal storage of a complex mixture of lipids,primarily cholesterol and glycosphingolipids.The NPC proteins regulate sterol homeostasis through production of LDL cholesterol-derived oxysterols.Oxysterols are endogenous ligands for the liver X receptors(LXRs),which can upregulate ATP binding cassette transporter A1(ABCA1) expression.ABCA1 may have antiatherogenic effects through the efflux of it-mediated cholesterol.Meanwhile,NPC1 heterozygote mutation confers substantial resistance to lesional necrosis and lesional macrophage apoptosis.Study of the NPC proteins will help us for further understanding of the mechanisms involved in atherogenesis.Niemann -pick protein C1 （NPC1） is a large integral membrane glycoprotein that resides in late endosomes, whereas niemann - pick protein C2 （ NPC2 ） is a small soluble protein found in the lumen of lysosomes. NPC1 protein is believed to facilitate the transport of lipids, particularly cholesterol, from late endosomes/lysosomes to the Golgi apparatus, endoplasmic reticulum and plasma membrane. NPC2 primarily plays a role in the egress of cholesterol and glycolipids from lysosomes. Mutations in either NPC1 or NPC2 result in aberrant lipid transport from endocytic compartments, which results in lysosomal storage of a complex mixture of lipids, primarily cholesterol and glycosphingolipids. The NPC proteins regulate sterol homeostasis through production of LDL cholesterol - derived oxysterols. Oxysterols are endogenous ligands for the liver X receptors（ LXRs）, which can upregulate ATP binding cassette transporter A1 （ABCA1） expression. ABCA1 may have antiatherogenic effects through the efflux of it - mediated cholesterol. Meanwhile, NPC1 heterozygote mutation confers substantial resistance to lesional necrosis and lesional macrophage apoptosis. Study of the NPC proteins will help us for further understanding of the mechanisms involved in atherogenesis.

关 键 词：C型尼曼-匹克蛋白1 C型尼曼-匹克蛋白2 ATP结合盒转运体 动脉硬化 

分 类 号：R363[医药卫生—病理学]