Moriwaki H, Kume N, Sawamura T, Aoyama T, Hoshikawa H, Ochi H, Nishi E, Masaki T, Kita T
Departments of Geriatric Medicine and Pharmacology, Graduate School of Medicine, Kyoto University, Japan.
Arterioscler Thromb Vasc Biol. 1998 Oct;18(10):1541-7. doi: 10.1161/01.atv.18.10.1541.
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 125I-labeled Ox-LDL but did not significantly degrade 125I-labeled acetylated LDL (Ac-LDL). Fucoidin and maleylated BSA (M-BSA), which inhibit 125I-Ox-LDL binding to class A scavenger receptors, did not inhibit 125I-Ox-LDL binding or degradation in LOX-1-CHO. Polyinosinic acid and carrageenan, in contrast, significantly reduced 125I-Ox-LDL binding to LOX-1-CHO by 62% and 60%, respectively. Delipidated and untreated 125I-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 125I-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.
氧化型低密度脂蛋白（Ox-LDL）及其脂质成分引发的内皮功能障碍或激活，已被证明在动脉粥样硬化的发病机制中起关键作用。我们最近在血管内皮细胞中鉴定出一种新型的Ox-LDL受体——凝集素样Ox-LDL受体（LOX-1）。为了检测LOX-1的配体特异性，我们建立了稳定表达人源和牛源LOX-1的CHO细胞系（LOX-1-CHO）。LOX-1-CHO能结合并降解125I标记的Ox-LDL，但对125I标记的乙酰化低密度脂蛋白（Ac-LDL）没有明显的降解作用。岩藻依聚糖和马来酰化牛血清白蛋白（M-BSA）可抑制125I-Ox-LDL与A类清道夫受体的结合，但对125I-Ox-LDL与LOX-1-CHO的结合或降解没有抑制作用。相反，聚肌苷酸和角叉菜胶分别使125I-Ox-LDL与LOX-1-CHO的结合显著降低了62%和60%。脱脂蛋白的和未处理的125I-Ox-LDL在LOX-1-CHO中被同等程度地结合和降解；此外，过量的未标记的、脱脂蛋白的Ox-LDL可抑制未处理的125I-Ox-LDL的结合和降解。综上所述，LOX-1是Ox-LDL的受体，而不是Ac-LDL的受体。LOX-1识别Ox-LDL的蛋白质部分，其配体特异性与其他Ox-LDL受体不同，包括A类和B类清道夫受体。
