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.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
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)
