Structure and Function of Receptors for Advanced Glycation End Products of the Maillard Reaction

年龄修饰蛋白受体（AGE-receptor）的特征在于其与衰老和疾病过程（如糖尿病并发症和动脉粥样硬化）的潜在联系。在本研究中，我们试图对巨噬细胞和血管平滑肌细胞的age受体进行表征，得到了以下结果从巨噬细胞来源的细胞系（RAW细胞）中纯化了四种age结合蛋白（90K,48K，28K和18K）。n -末端分析表明，其中3个是已知的蛋白，28k蛋白是一个新蛋白。后者正在被分析巨噬细胞清除受体（macrophage scavenger receptor， MSR）已被Kodama等克隆。过表达MSR c-DNA的CHO细胞（CHO- srii细胞）不仅对乙酰- ldl （MSR的配体），而且对AGE-BSA也表现出增强的内吞摄取。乙酰低密度脂蛋白可有效抑制这些细胞对AGE-BSA的内吞摄取。此外，从MSR基因敲除小鼠中获得的常驻腹膜巨噬细胞降解AGE-BSA的能力显着降低，与从野生型产仔中获得的巨噬细胞相比，下降了不到30%。这些数据表明，MSR在巨噬细胞或巨噬细胞衍生细胞对age蛋白的内吞摄取中起主要作用这项研究是由我们对人类动脉粥样硬化病变晚期平滑肌细胞衍生泡沫细胞中age积累的免疫学论证发起的。兔主动脉平滑肌细胞（SMC）具有高亲和力的age蛋白结合位点。age蛋白被SMC内吞并诱导SMC的细胞迁移（趋化性）。由于乙酰- ldl不影响这些SMC对age -蛋白的内吞噬，也不影响age -蛋白诱导的趋化性，这表明SMC表达的age -受体与MSR不同。配体印迹分析鉴定出一个200kd蛋白。我们现在正在测定部分氨基酸序列。

The receptor for AGE-modified proteins (AGE-receptor) has been characterized from its potential link to aging and disease processes such as diabetic complications and atherosclerosis. In the present study, we attempted to characterize the AGE-receptor of macrophages and vascular smooth muscle cells and the following results were obtained.[1] Four AGE-binding proteins (90K,48K,28K & 18K) were purified from macrophage-derived cell line (RAW cells). N-Terminal analyzes indicated that three of them were ones already known, and 28K-protein was a novel one. The latter is being analyzed.[2] The macrophage scavenger receptor (MSR) was already cloned by Kodama et al. CHO cells overexpressing MSR c-DNA (CHO-SRII cells) showed and enhanced endocytic uptake not only for acetyl-LDL (a ligand for MSR), but also for AGE-BSA.The endocytic uptake of AGE-BSA by these cells were effectively inhibited by acetyl-LDL.Furthermore, resident peritoneal macrophages obtained from MSR gene-knockout mice showed a marked reduction in their capacity to degrade AGE-BSA,less than 30% compared with those obtained from wild type litter mates. These data suggest that MSR plays a major role in the endocytic uptake of AGE-proteins by macrophages or macrophage-derived cells.[3] This study was initiated by our immunological demonstration of the AGE-accumulation in smooth muscle cells-derived foam cells in the advanced stage of human atherosclerotic lesions. Smooth muscel cells (SMC) from rabbit aorta possessed a high-affinity binding site for AGE-proteins. AGE-proteins underwent endocytic uptake by SMC and induced the cell migration (chemotaxis) of these SMC.Since acetyl-LDL did not affect the endocytic uptake of AGE-proteins by these SMC nor the AGE-proteins-induced chemotaxis, it is suggested that the AGE-receptor expressed by SMC differs from MSR.The ligand blotting analysis identified a 200Kd-protein. We are now determining partial amino acid sequences.