Scavenger receptor class B type I as a receptor for oxidized low density lipoprotein.
Scavenger receptor class B type I as a receptor for oxidized low density lipoprotein.
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DOI：
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发表时间：
2001-09
影响因子：
6.5
通讯作者：
K. Gillotte-Taylor;A. Boullier;J. L. Witztum;D. Steinberg;O. Quehenberger
中科院分区：
文献类型：
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作者：
K. Gillotte-Taylor;A. Boullier;J. L. Witztum;D. Steinberg;O. Quehenberger
I型B类清道夫受体（SR-BI）已被确定为脂质从HDL选择性转移至哺乳动物细胞的主要介体。除了其在胆固醇代谢中的作用之外，SR-BI还显示出结合凋亡细胞，因此在理论上也可以作为清道夫受体起作用。我们现在表明，SR-BI以高亲和力（K（d）为4.0 +/- 0.5 μ g/ml）结合氧化LDL（OxLDL），并在与其他清道夫受体相当的程度上介导内化和降解，当归一化为结合活性时。OxLDL与SR-BI结合的最佳竞争者是氧化脂蛋白，而天然或乙酰化脂蛋白仅竞争一小部分OxLDL结合。从OxLDL中分离的脂质和分离的蛋白质都与SR-BI具有高亲和力结合，并表现出部分相互竞争。单克隆抗体EO 6，一种抗氧化磷脂的抗体，和1-棕榈酰-2-（5-氧代戊酰）磷脂酰胆碱（POVPC）与完整OxLDL和从OxLDL分离的脂质有效竞争SR-BI结合。通过巨噬细胞介导OxLDL的内化，并表明氧化磷脂在此过程中起着重要作用。
Scavenger receptor class B type I (SR-BI) has been established as the primary mediator of the selective transfer of lipids from HDL to mammalian cells. In addition to its role in cholesterol metabolism, SR-BI has been shown to bind apoptotic cells and thus could in theory also function as a scavenger receptor. We now show that SR-BI binds oxidized LDL (OxLDL) with high affinity (K(d) of 4.0 +/- 0.5 microg/ml) and mediates internalization and degradation to an extent comparable to that of other scavenger receptors, when normalized to binding activity. The best competitors for OxLDL binding to SR-BI were oxidized lipoproteins, whereas native or acetylated lipoproteins only competed for a small fraction of OxLDL binding. Both the isolated lipids and the isolated protein from OxLDL bound with high affinity to SR-BI and showed partial reciprocal competition. Monoclonal antibody EO6, an antibody against oxidized phospholipids, and 1-palmitoyl-2-(5-oxovaleroyl) phosphatidylcholine (POVPC) both competed effectively with intact OxLDL and with isolated lipids from OxLDL for SR-BI binding.Together, these results demonstrate a potential function of SR-BI, in addition to its role in selective uptake of lipids, to mediate internalization of OxLDL by macrophages and suggest a central role for oxidized phospholipids in this process.