Sphingomyelin-dependence of cholesterol efflux mediated by ABCG1

被引:58
|
作者
Sano, Osamu
Kobayashi, Aya
Nagao, Kohjiro
Kumagai, Keigo
Kioka, Noriyuki
Hanada, Kentaro
Ueda, Kazumitsu [1 ]
Matsuo, Michinori
机构
[1] Kyoto Univ, Grad Sch Architecture, Biochem Cellular Lab, Div Appl Life Sci, Kyoto 606, Japan
[2] Inst Natl Infect Dis, Dept Biochem & Cell Biol, Tokyo 162, Japan
关键词
ATP binding cassette A1; ceramide transfer protein; detergent-resistant membrane; raft;
D O I
10.1194/jlr.M700139-JLR200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
ABCG1, one of the half-type ATP binding cassette (ABC) proteins, mediates the efflux of cholesterol to HDL and functions in the reverse cholesterol transport from peripheral cells to the liver. We have shown that ABCG1 mediates the efflux of not only cholesterol but also sphingomyelin (SM) and phosphatidylcholine. Because SM preferentially associates with cholesterol, we examined whether it plays an important role in the ABCG1-mediated efflux of cholesterol. The efflux of cholesterol and SM mediated by ABCG1 was reduced in a mutant CHO-K1 cell line, LY-A, in which the cellular SM level is reduced because of a mutation of the ceramide transfer protein CERT. In contrast, CHO-K1 cells overexpressing CERT showed an increased efflux of cholesterol and SM mediated by ABCG1. The sensitivity of cells to methyl-beta-cyclodextrin suggested that cholesterol in nonraft domains was increased due to the disruption of raft domains in LY-A cells. These results suggest that the ABCG1-mediated efflux of cholesterol and SM is dependent on the cellular SM level and distribution of cholesterol in the plasma membrane.
引用
收藏
页码:2377 / 2384
页数:8
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