文章基本信息

标题：ABCA1 and ABCG1 or ABCG4 act sequentially to remove cellular cholesterol and generate cholesterol-rich HDL
本地全文：下载
作者：Vaughan, Ashley M. ; Oram, John F.
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2006
卷号：47
期号：11
页码：2433-2443
DOI：10.1194/jlr.M600218-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Recent developments in lipid metabolism have shown the importanceof ATP binding cassette transporters (ABCs) in controlling cellularand total body lipid homeostasis. ABCA1 mediates the transportof cholesterol and phospholipids from cells to lipid-poor apolipoproteinA-I (apoA-I), whereas ABCG1 and ABCG4 mediate the transportof cholesterol from cells to lipidated lipoproteins. ABCA1,ABCG1, and ABCG4 are all expressed in cholesterol-loaded macrophages,and macrophages from ABCA1 and ABCG1 knockout mice accumulatecholesteryl esters. Here, we show that the lipidated particlesgenerated by incubating cells overexpressing ABCA1 with apoA-Iare efficient acceptors for cholesterol released from cellsoverexpressing either ABCG1 or ABCG4. The cholesterol releasedto the particles was derived from a cholesterol oxidase-accessibleplasma membrane pool in both ABCG1 and ABCG4 cells, which isthe same pool of cholesterol shown previously to be removedby high density lipoproteins. ABCA1 cells incubated with apoA-Igenerated two major populations of cholesterol- and phospholipid-richlipoprotein particles that were converted by ABCG1 or ABCG4cells to one major particle population that was highly enrichedin cholesterol. These results suggest that ABCG1 and ABCG4 actin concert with ABCA1 to maximize the removal of excess cholesterolfrom cells and to generate cholesterol-rich lipoprotein particles. Supplementary key words ATP binding cassette transporter A1 • ATP binding cassette transporter G1 • ATP binding cassette transporter G4 • high density lipoprotein