Ligand specificity of LOX-1, a novel endothelial receptor for oxidized low density lipoprotein
Ligand specificity of LOX-1, a novel endothelial receptor for oxidized low density lipoprotein
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DOI：
10.1161/01.atv.18.10.1541
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发表时间：
1998-10-01
影响因子：
8.7
通讯作者：
Kita, T
中科院分区：
文献类型：
--
作者：
Moriwaki, H;Kume, N;Kita, T
氧化型低密度脂蛋白（Ox-LDL）及其脂质成分引起的内皮功能障碍或激活在动脉粥样硬化的发病机制中起关键作用。我们最近发现了一种新的受体Ox-LDL-指定凝集素样Ox-LDL，受体（LOX-1）在血管内皮细胞。为了检测LOX-1的配体特异性，我们建立了稳定表达人和牛LOX-1的CHO细胞系（LOX-1-CHO）。LOX-1-CHO结合并降解I-125标记的Ox-LDL，但不显著降解I-125标记的乙酰化LDL（Ac-LDL）。抑制I-125-Ox-LDL与A类清道夫受体结合的岩藻多糖和马来酰化BSA（M-BSA）在LOX-1-CHO、聚肌胞酸和角叉菜胶中不抑制I-125-Ox-LDL结合或降解，相反，显著降低I-125-Ox-LDL与LOX-1-CHO的结合;分别降低62%和60%：脱脂和未处理的I-125-Ox-LDL在LOX-1-CHO中的结合和降解相同;此外，过量的未标记的脱脂Ox-LDL抑制未处理的I-125-Ox-LDL的结合和降解。总之，LOX-1是Ox-LDL的受体，但不是Ac-LDL的受体。LOX-1识别Ox-LDL的蛋白质部分，并且其配体特异性不同于Ox-LDL的其它受体，包括A类和B类清道夫受体。
Endothelial dysfunction, or activation, elicited by oxidized low density lipoprotein (Ox-LDL) and its lipid constituents has been shown to play a key role in the pathogenesis of atherosclerosis. We recently have identified a novel receptor for Ox-LDL-designated lectin-like Ox-LDL, receptor(LOX-1) in vascular endothelial cells. To examine ligand specificity of LOX-1, we established CHO cell lines stably expressing both human and bovine LOX-1 (LOX-1-CHO). LOX-1-CHO bound and degraded I-125-labeled Ox-LDL but did not significantly degrade I-125-labeled acetylated LDL (Ac-LDL). Fucoidin and maleylated BSA (M-BSA), which inhibit I-125-Ox-LDL binding to class A scavenger receptors, did not inhibit I-125-Ox-LDL binding or degradation in LOX-1-CHO, Polyinosinic acid and carrageenan, in contrast, significantly reduced I-125-Ox-LDL binding to LOX-1-CHO;by 62% and 60%, respectively: Delipidated and untreated I-125-Ox-LDL were bound and degraded equally in LOX-1-CHO; furthermore, excess amounts of unlabeled, delipidated Ox-LDL inhibited binding and degradation of untreated I-125-Ox-LDL. Taken together, LOX-1 is a receptor for Ox-LDL but not for Ac-LDL. LOX-1 recognizes protein moiety of Ox-LDL, and its ligand specificity is distinct from other receptors for Ox-LDL, including class A and B scavenger receptors.