Horiuchi S, Higashi T, Ikeda K, Saishoji T, Jinnouchi Y, Sano H, Shibayama R, Sakamoto T, Araki N
Department of Biochemistry, Kumamoto University School of Medicine, Japan.
Diabetes. 1996 Jul;45 Suppl 3:S73-6. doi: 10.2337/diab.45.3.s73.
Modification of proteins by long-term incubation with glucose leads to the formation of advanced glycation end products (AGEs). AGE proteins are taken up by macrophages via the AGE receptor, which is similar to the macrophage scavenger receptor (MSR). In the present study, we compared the ligand specificity of the AGE receptor with that of MSR by three different experiments. The endocytic uptake of 125I-acetyl-LDL by RAW cells was effectively inhibited by unlabeled AGE-bovine serum albumin (BSA), whereas the inhibitory effect of acetyl-LDL on 125I-AGE-BSA was partial. Polyanions showing an effective inhibition for endocytic uptake of AGE-BSA were not always inhibitory for endocytic degradation of acetyl-LDL. These data, together with those obtained by three-dimensional fluorescence-activated cell sorter analysis, indicate that AGE proteins are recognized by more than two receptors, of which MSR is at least one. Finally, we examined whether MSR could mediate the endocytic uptake of AGE proteins by Chinese hamster ovary cells overexpressing bovine type II MSR (CHO-SRII cells). 125I-AGE-BSA underwent endocytic degradation by CHO-SRII cells, and this was effectively inhibited by unlabeled acetyl-LDL. These results clearly show that MSR mediates the endocytic uptake of AGE proteins, suggesting a new role of MSR in biological recognition of AGE in vivo.
蛋白质与葡萄糖长期孵育会导致晚期糖基化终末产物（AGEs）的形成。AGE蛋白通过AGE受体被巨噬细胞摄取，该受体与巨噬细胞清道夫受体（MSR）相似。在本研究中，我们通过三个不同的实验比较了AGE受体与MSR的配体特异性。未标记的AGE-牛血清白蛋白（BSA）可有效抑制RAW细胞对125I-乙酰低密度脂蛋白（LDL）的内吞摄取，而乙酰-LDL对125I-AGE-BSA的抑制作用则是部分性的。对AGE-BSA内吞摄取有有效抑制作用的聚阴离子并不总是对乙酰-LDL的内吞降解有抑制作用。这些数据，连同通过三维荧光激活细胞分选分析获得的数据，表明AGE蛋白可被两种以上的受体识别，其中MSR至少是其中之一。最后，我们检测了MSR是否能介导过表达牛II型MSR的中国仓鼠卵巢细胞（CHO-SRII细胞）对AGE蛋白的内吞摄取。125I-AGE-BSA可被CHO-SRII细胞进行内吞降解，且未标记的乙酰-LDL可有效抑制这种降解。这些结果清楚地表明MSR介导了AGE蛋白的内吞摄取，提示MSR在体内AGE的生物学识别中具有新的作用。
