Specific oxidized phospholipids inhibit scavenger receptor BI-mediated selective uptake of cholesteryl esters
Specific oxidized phospholipids inhibit scavenger receptor BI-mediated selective uptake of cholesteryl esters
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DOI：
10.1074/jbc.m710474200
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发表时间：
2008-04-18
影响因子：
4.8
通讯作者：
Podrez, Eugene A.
中科院分区：
文献类型：
--
作者：
Ashraf, Mohammad Z.;Kar, Niladri S.;Podrez, Eugene A.
我们最近已经证明，特定的氧化磷脂（oxPC（CD 36））在体内的氧化应激部位，如动脉粥样硬化病变，高脂血症血浆，血浆中的低高密度脂蛋白水平的积累。oxPC（CD 36）作为清道夫受体CD 36的高亲和力配体，介导巨噬细胞对氧化低密度脂蛋白的摄取，并通过血小板清道夫受体CD 36促进血栓形成前状态。我们现在报告oxPC（CD 36）代表清道夫受体类B，I型（SR-BI）的另一个成员的配体。oxPC（CD 36）阻止其生理配体高密度脂蛋白与SR-BI结合，因为SR-BI上这两种配体的结合位点非常接近。此外，oxPC（CD 36）干扰SR-BI介导的肝细胞中胆固醇酯的选择性摄取。因此，氧化应激和血浆中特定氧化磷脂的蓄积可能对胆固醇逆向转运具有抑制作用。
We have recently demonstrated that specific oxidized phospholipids (oxPC(CD36)) accumulate at sites of oxidative stress in vivo such as within atherosclerotic lesions, hyperlipidemic plasma, and plasma with low high-density lipoprotein levels. oxPC(CD36) serve as high affinity ligands for the scavenger receptor CD36, mediate uptake of oxidized low density lipoprotein by macrophages, and promote a pro-thrombotic state via platelet scavenger receptor CD36. We now report that oxPC(CD36) represent ligands for another member of the scavenger receptor class B, type I (SR-BI). oxPC(CD36) prevent binding to SR-BI of its physiological ligand, high density lipoprotein, because of the close proximity of the binding sites for these two ligands on SR-BI. Furthermore, oxPC(CD36) interfere with SR-BI-mediated selective uptake of cholesteryl esters in hepatocytes. Thus, oxidative stress and accumulation of specific oxidized phospholipids in plasma may have an inhibitory effect on reverse cholesterol transport.