Mehta J L, Li D Y
Department of Medicine, University of Florida, Gainesville, USA.
Biochem Biophys Res Commun. 1998 Jul 30;248(3):511-4. doi: 10.1006/bbrc.1998.9004.
Although macrophages scavenge oxidatively modified low density lipoprotein (ox-LDL) via specific receptors, the uptake of ox-LDL by endothelial cells is thought to be mediated by a different receptor (LOX-1). We examined the presence of LOX-1 on cultured human coronary artery endothelial cells (HCAECs) by RT-PCR, radioligand blot, and binding assays. LOX-1 mRNA and protein were consistently identified in HCAECs. [125I]-ox-LDL binding assay also identified high affinity binding sites for LOX-1 on HCAECs (KD: 1.71 x 10(-8) M: Bmax: 29.7 ng/mg protein). There was no change in LOX-1 expression in HCAECs treated with native-LDL. In contrast, incubation of HCAECs with ox-LDL (10-40 micrograms/ml) increased LOX-1 expression (mRNA and protein). The upregulation of LOX-1 expression appeared to be dependent on ox-LDL concentration. Higher concentration (100 micrograms/ml) however, decreased LOX-1 expression, perhaps related to its cytotoxic effect. These observations indicate that ox-LDL upregulates its own receptor on HCAECs. This phenomenon may explain enhanced uptake of ox-LDL by HCAECs in hyperlipidemia resulting in cellular dysfunction.
尽管巨噬细胞通过特定受体清除氧化修饰的低密度脂蛋白（ox-LDL），但内皮细胞对ox-LDL的摄取被认为是由另一种受体（凝集素样氧化型低密度脂蛋白受体-1，LOX-1）介导的。我们通过逆转录聚合酶链反应（RT-PCR）、放射性配体印迹和结合试验检测了培养的人冠状动脉内皮细胞（HCAECs）上LOX-1的存在情况。在HCAECs中持续鉴定出LOX-1 mRNA和蛋白。[125I]-ox-LDL结合试验也鉴定出HCAECs上存在LOX-1的高亲和力结合位点（解离常数KD：1.71×10(-8) M；最大结合容量Bmax：29.7 ng/mg蛋白）。用天然低密度脂蛋白（native-LDL）处理的HCAECs中，LOX-1的表达没有变化。相反，用ox-LDL（10 - 40微克/毫升）孵育HCAECs会增加LOX-1的表达（mRNA和蛋白）。LOX-1表达的上调似乎依赖于ox-LDL的浓度。然而，更高浓度（100微克/毫升）会降低LOX-1的表达，这可能与其细胞毒性作用有关。这些观察结果表明，ox-LDL上调了其在HCAECs上自身的受体。这种现象可能解释了高脂血症中HCAECs对ox-LDL摄取增加导致细胞功能障碍的原因。
