文章基本信息

标题：Intracellular cholesterol transport proteins enhance hydrolysis of HDL-CEs and facilitate elimination of cholesterol into bile
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作者：Jing Wang ; Jinghua Bie ; Shobha Ghosh 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2016
卷号：57
期号：9
页码：1712-1719
DOI：10.1194/jlr.M069682
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：While HDL-associated unesterified or free cholesterol (FC) is thought to be rapidly secreted into the bile, the fate of HDL-associated cholesteryl esters (HDL-CEs) that represent >80% of HDL-cholesterol, is only beginning to be understood. In the present study, we examined the hypothesis that intracellular cholesterol transport proteins [sterol carrier protein 2 (SCP2) and fatty acid binding protein-1 (FABP1)] not only facilitate CE hydrolase-mediated hydrolysis of HDL-CEs, but also enhance elimination of cholesterol into bile. Adenovirus-mediated overexpression of FABP1 or SCP2 in primary hepatocytes significantly increased hydrolysis of HDL-[³H]CE, reduced resecretion of HDL-CE-derived FC as nascent HDL, and increased its secretion as bile acids. Consistently, the flux of [³H]cholesterol from HDL-[³H]CE to biliary bile acids was increased by overexpression of SCP2 or FABP1 in vivo and reduced in SCP2^−/− mice. Increased flux of HDL-[³H]CE to biliary FC was noted with FABP1 overexpression and in SCP2^−/− mice that have increased FABP1 expression. Lack of a significant decrease in the flux of HDL-[³H]CE to biliary FC or bile acids in FABP1^−/− mice indicates the likely compensation of its function by an as yet unidentified mechanism. Taken together, these studies demonstrate that FABP1 and SCP2 facilitate the preferential movement of HDL-CEs to bile for final elimination.
关键词：cholesterol elimination ; hepatocyte ; reverse cholesterol transport ; bile acid secretion ; high density lipoprotein ; cholesteryl esters ; sterol carrier protein 2 ; fatty acid binding protein-1