文章基本信息

标题：Redistribution of macrophage cholesteryl ester hydrolase from cytoplasm to lipid droplets upon lipid loading
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作者：Zhao, Bin ; Fisher, Bernard J. ; Clair, Richard W. St. 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：2005
卷号：46
期号：10
页码：2114-2121
DOI：10.1194/jlr.M500207-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Hydrolysis of intracellular cholesteryl esters (CEs) representsthe first step in the removal of cholesterol from lipid-ladenfoam cells associated with atherosclerotic lesions. Neutralcholesteryl ester hydrolase (CEH) catalyzes this reaction, andwe recently cloned the cDNA for the human macrophage CEH anddemonstrated increased mobilization of intracellular CE dropletsby CEH overexpression. The present study was undertaken to testthe hypothesis that for CE hydrolysis, CEH must become associatedwith the surface of the cytoplasmic lipid droplets. Our datashow the redistribution of CEH from cytosol to lipid dropletsupon lipid loading of human THP-1 macrophages. Depletion oftriacylglycerol (TG) by incubation with the acyl-CoA synthetaseinhibitor Triacsin D had no effect on CEH association with thelipid droplets, suggesting that CEH associates with mixed (CE+ TG) as well as TG-depleted CE droplets. However, CEH had 2.5-foldhigher activity when mixed droplets were used as substrate inan in vitro assay, consistent with the reported higher cholesterolefflux from cells containing mixed isotropic droplets. Perilipinas well as adipophilin, two lipid droplet-associated proteins,were also present on the lipid droplets in THP-1 macrophages. In conclusion, CEH associates with its intracellular substrate(lipid droplets) and hydrolyzes CE more efficiently from mixeddroplets. Supplementary key words perilipin • adipophilin • THP-1 macrophages