title: NPC1, intracellular cholesterol trafficking and atherosclerosis.
abstract: 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.
authors.affiliation: Life Science Research Center, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Xiao-Hua
authors.initials: XH
authors.lastname: Yu
authors.affiliation: Department of Electrocardiogram, the Second Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Na
authors.initials: N
authors.lastname: Jiang
authors.affiliation: Department of Intensive Care, the Affiliated Nanhua Hospital, University of South China, Hengyang, Hunan 421001, China.
authors.forename: Ping-Bo
authors.initials: PB
authors.lastname: Yao
authors.affiliation: Department of Biochemistry and Molecular Biology, The Libin Cardiovascular Institute of Alberta, The University of Calgary, Health Sciences Center, 3330 Hospital Dr NW, Calgary, Alberta, T2N 4 N1, Canada.
authors.forename: Xi-Long
authors.initials: XL
authors.lastname: Zheng
authors.affiliation: Department of Physiology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Cayabyab
authors.affiliation: Life Science Research Center, University of South China, Hengyang, Hunan 421001, China; Institute of Cardiovascular Research, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan 421001, China. Electronic address: tangchaoke@qq.com.
authors.forename: Chao-Ke
authors.initials: CK
authors.lastname: Tang
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D042541:Intracellular Space / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000378:metabolism / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D002784:Cholesterol
keywords: ABCA1; ATP-binding cassette transporter A1; Atherosclerosis; COX-2; Cholesterol; DHC; ER; ERK1/2; LDL; LDL-C; LDL-cholesterol; LDLR; LE/LY; LXR; N-terminal domain; NPC1; NPC2; NTD; Niemann-Pick type C1; ORP5; OSBP; OSBP­related protein 5; PPARα; SREBP; SSD; TGN; apoA-I; apoE; apolipoprotein A-I; apolipoprotein E; cyclooxygenase-2; dihydrocapsaicin; endoplasmic reticulum; extracellular signal-regulated kinase 1/2; late endosome/lysosome; liver X receptor; low-density lipoprotein; low-density lipoprotein receptor; oxLDL; oxidized low-density lipoprotein; oxysterol­binding protein; peroxisome proliferator-activated receptor α; sterol regulatory element-binding protein; sterol-sensing domain; trans-Golgi network