Efflux of sphingomyelin, cholesterol, and phosphatidylcholine by ABCG1
Efflux of sphingomyelin, cholesterol, and phosphatidylcholine by ABCG1
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DOI：
10.1194/jlr.m500546-jlr200
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发表时间：
2006-08-01
影响因子：
6.5
通讯作者：
Matsuo, Michinori
中科院分区：
文献类型：
--
作者：
Kobayashi, Aya;Takanezawa, Yasukazu;Matsuo, Michinori
胆固醇和磷脂对身体是必不可少的，但过量的胆固醇或脂类是有毒的，是动脉硬化的风险因素。Abcg1是一种半型ABC蛋白，被认为参与胆固醇的动态平衡。为了探索Abcg1在胆固醇动态平衡中的作用，我们研究了它的亚细胞定位和功能。Abcg1和Walkera赖氨酸突变体Abcg1-K120M定位于稳定表达Abcg1的HEK293细胞的质膜上，并形成同源二聚体。在BSA存在的情况下，稳定表达Abcg1的转化子表现出胆固醇和胆碱磷脂的外流，高密度脂蛋白的存在增加了胆固醇的外流，而表达Abcg1-K120M的细胞没有增加胆固醇外流，这表明外流需要ATP结合和/或水解。MS和TLC分析表明，Abcg1和ABCA1可分泌多种鞘磷脂(SM)和磷脂酰胆碱(PC)，其中SM由Abcg1优先分泌，而PC由ABCA1优先分泌。这些结果表明，ABCA1和Abcg1以不同的机制介导了不同种类的磷脂的分泌，并协同作用于外周细胞中胆固醇和磷脂的清除。
Cholesterol and phospholipids are essential to the body, but an excess of cholesterol or lipids is toxic and a risk factor for arteriosclerosis. ABCG1, one of the halftype ABC proteins, is thought to be involved in cholesterol homeostasis. To explore the role of ABCG1 in cholesterol homeostasis, we examined its subcellular localization and function. ABCG1 and ABCG1-K120M, a WalkerA lysine mutant, were localized to the plasma membrane in HEK293 cells stably expressing ABCG1 and formed a homodimer. A stable transformant expressing ABCG1 exhibited efflux of cholesterol and choline phospholipids in the presence of BSA, and the cholesterol efflux was enhanced by the presence of HDL, whereas cells expressing ABCG1-K120M did not, suggesting that ATP binding and/or hydrolysis is required for the efflux. Mass and TLC analyses revealed that ABCG1 and ABCA1 secrete several species of sphingomyelin (SM) and phosphatidylcholine (PC), and SMs were preferentially secreted by ABCG1, whereas PCs were preferentially secreted by ABCA1. These results suggest that ABCA1 and ABCG1 mediate the lipid efflux in different mechanisms, in which different species of phospholipids are secreted, and function coordinately in the removal of cholesterol and phospholipids from peripheral cells.