NPC1, intracellular cholesterol trafficking and atherosclerosis
详细信息 查看全文
- 作者：Xiao-Hua Yu ; Na Jiang ; Ping-Bo Yao ; Xi-Long Zheng ; Francisco S. Cayabyab ; Chao-Ke Tang
- 关键词：NPC1 ; Niemann-Pick type C1 ; LE/LY ; late endosome/lysosome ; LDL ; low-density lipoprotein ; LDL-C ; LDL-cholesterol ; ER ; endoplasmic reticulum ; SSD ; sterol-sensing domain ; NTD ; N-terminal domain ; apoE ; apolipoprotein E ; LXR ; liver X receptor ; OSBP ; oxysterol ; binding protein ; ORP5 ; OSBP ; related protein 5 ; TGN ; trans-Golgi network ; oxLDL ; oxidized low-density lipoprotein ; ERK1/2 ; extracellular signal-regulated kinase 1/2 ; COX-2 ; cyclooxygenase-2 ; PPAR伪 ; peroxisome proliferator-activated recep
- 刊名：Clinica Chimica Acta
- 出版年：15 February, 2014
- 年：2014
- 卷：429
- 期：Complete
- 页码：69-75
- 全文大小：889 K
文摘
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颅binding protein (OSBP)颅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.