Temporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of ABCA1 during nascent HDL generation.
Temporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of ABCA1 during nascent HDL generation.
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DOI：
10.1038/s41598-018-24428-6
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发表时间：
2018-04-18
影响因子：
4.6
通讯作者：
Ueda K
中科院分区：
文献类型：
--
作者：
Ishigami M;Ogasawara F;Nagao K;Hashimoto H;Kimura Y;Kioka N;Ueda K
血浆中高密度脂蛋白（HDL）的质量和数量对预防冠状动脉疾病具有重要意义。atp结合盒蛋白A1 （ABCA1）和载脂蛋白A-I （apoA-I）在新生HDL形成中起重要作用，但关于新生HDL产生的机制仍存在争议。在“直接加载模型”中，apoA-I在与转运体结合时直接从ABCA1获取脂质。相比之下，在“间接模型”中，apoA-I从ABCA1产生的特定膜结构域获取脂质。在本研究中，我们发现胰蛋白酶处理引起BHK/ABCA1细胞中磷脂酰胆碱（PC）和胆固醇的快速释放，并且脂质释放的时间过程与胰蛋白酶消化ABCA1表面细胞外结构域（ECDs）和ECD片段释放到培养基中的时间过程一致。这种胰蛋白酶依赖的脂质释放依赖于ABCA1 atp酶活性，并没有发生在表达ABCG1的细胞中，ABCG1像ABCA1一样输出脂质，但没有大的ecd。这些结果表明，细胞表面的胰蛋白酶敏感位点是ABCA1的大ecd，并且在新生的HDL形成过程中，由ABCA1运输的脂质暂时被隔离在ecd内。
The quality and quantity of high-density lipoprotein (HDL) in blood plasma are important for preventing coronary artery disease. ATP-binding cassette protein A1 (ABCA1) and apolipoprotein A-I (apoA-I) play essential roles in nascent HDL formation, but controversy persists regarding the mechanism by which nascent HDL is generated. In the “direct loading model”, apoA-I acquires lipids directly from ABCA1 while it is bound to the transporter. By contrast, in the “indirect model”, apoA-I acquires lipids from the specific membrane domains created by ABCA1. In this study, we found that trypsin treatment causes rapid release of phosphatidylcholine (PC) and cholesterol from BHK/ABCA1 cells, and that the time course of lipid release coincides with those of trypsin digestion of extracellular domains (ECDs) of surface ABCA1 and of release of ECD fragments into the medium. This trypsin-dependent lipid release was dependent on ABCA1 ATPase activity, and did not occur in cells that express ABCG1, which exports lipids like ABCA1 but does not have large ECDs. These results suggest that the trypsin-sensitive sites on the cell surface are the large ECDs of ABCA1, and that lipids transported by ABCA1 are temporarily sequestered within the ECDs during nascent HDL formation.
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影响因子：
6.5
作者：
Duong, PT;Collins, HL;Phillips, MC
通讯作者：
Phillips, MC
影响因子：
64.5
作者：
Qian, Hongwu;Zhao, Xin;Gong, Xin
通讯作者：
Gong, Xin
影响因子：
30.8
作者：
Bodzioch, M;Orsó, E;Schmitz, G
通讯作者：
Schmitz, G
DOI：
10.1016/j.bbrc.2009.02.161
发表时间：
2009-04-24
影响因子：
3.1
作者：
Azuma, Yuya;Takada, Mie;Ueda, Kazumitsu
通讯作者：
Ueda, Kazumitsu
影响因子：
14.9
作者：
Drozdetskiy A;Cole C;Procter J;Barton GJ
通讯作者：
Barton GJ