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

AGE修饰蛋白的受体（AGE受体）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，我们试图表征巨噬细胞和血管平滑肌细胞的AGE受体，并获得以下结果。[1]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（90 K、48 K、28 K和18 K）。N-末端分析表明，其中3个蛋白是已知的，28 K蛋白是一个新的蛋白。后者正在分析中。[2]巨噬细胞清道夫受体（MSR）已被Kodama等人克隆。（CHO-SRII细胞）显示并增强内吞摄取不仅乙酰-LDL乙酰化低密度脂蛋白（acetyl-LDL）能有效地抑制这些细胞对AGE-BSA的内吞摄取。从MSR基因敲除小鼠获得的常驻腹腔巨噬细胞显示出它们降解AGE-BSA的能力显著降低，与从野生型同窝出生的小鼠获得的那些相比，低于30%。这些数据表明，MSR在巨噬细胞或巨噬细胞衍生的细胞对AGE蛋白的内吞摄取中起着重要作用。[3]这项研究是由我们的免疫学证明在人类动脉粥样硬化病变的晚期阶段，在平滑肌细胞衍生的泡沫细胞中的AGE积累开始的。兔主动脉平滑肌细胞（SMC）具有与AGE蛋白的高亲和力结合位点。SMC对AGE蛋白的内吞摄取和对AGE蛋白的趋化作用均不受乙酰化低密度脂蛋白的影响，提示SMC表达的AGE受体不同于MSR。我们现在正在确定部分氨基酸序列。

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.