MACROPHAGE SCAVENGER RECEPTOR MEDIATES THE ENDOCYTIC UPTAKE AND DEGRADATION OF ADVANCED GLYCATION END-PRODUCTS OF THE MAILLARD REACTION
MACROPHAGE SCAVENGER RECEPTOR MEDIATES THE ENDOCYTIC UPTAKE AND DEGRADATION OF ADVANCED GLYCATION END-PRODUCTS OF THE MAILLARD REACTION
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DOI：
10.1111/j.1432-1033.1995.0408h.x
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发表时间：
1995-06-01
期刊：
影响因子：
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通讯作者：
HORIUCHI, S
中科院分区：
文献类型：
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作者：
ARAKI, N;HIGASHI, T;HORIUCHI, S
通过与葡萄糖长期孵育修饰蛋白质导致晚期糖基化终产物（AGE）的形成。最近在几种人体组织中存在的AGE蛋白的免疫学证明表明，它们可能与衰老、糖尿病并发症和动脉粥样硬化有关。AGE蛋白通过AGE受体被巨噬细胞吸收，AGE受体类似于巨噬细胞清道夫受体（MSR）。在本研究中，我们利用过表达牛II型MSR （CHO- srii）的中国仓鼠卵巢（CHO）细胞，研究MSR是否介导AGE蛋白的内吞摄取。i -125标记的AGE牛血清白蛋白（I-125-AGE-BSA）和i -125乙酰化低密度脂蛋白（I-125-acetyl-LDL）被CHO- srii细胞内吞降解，但不被对照CHO细胞降解。未标记的AGE-BSA和acetyl-LDL显著抑制CHO-SRII细胞对I-125-acetyl-LDL和I-125-AGE-BSA的内降解，使用与金颗粒结合的AGE-BSA和抗（牛MSR）抗体（D2）的免疫电镜研究显示，金颗粒和抗体的反应位点在质膜的包被凹坑和内体中共定位。这些结果清楚地表明，MSR介导了AGE蛋白的内吞摄取和降解，提示MSR在体内对AGE的生物识别中具有新的作用。
Modification of proteins by long-term incubation with glucose leads to the formation of advanced glycation end products (AGE). Recent immunological demonstration of the presence of AGE proteins in several human tissues suggests that they may be involved in aging, diabetic complications and atherosclerosis. 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 examined whether MSR could mediate the endocytic uptake of AGE proteins by using Chinese hamster ovary (CHO) cells overexpressing bovine type II MSR (CHO-SRII). I-125-labelled AGE bovine serum albumin (I-125-AGE-BSA) as well as I-125-acetylated low-density lipoprotein (I-125-acetyl-LDL) underwent endocytic degradation by CHO-SRII cells, but not by control CHO cells. Endocytic degradation of I-125-acetyl-LDL and I-125-AGE-BSA by CHO-SRII cells was significantly inhibited by unlabeled AGE-BSA, as well as by acetyl-LDL, Immunoelectron microscopic studies using both AGE-BSA conjugated with gold particles and anti-(bovine MSR) antibody (D2) revealed co-localization of gold particles and the reactive sites for the antibody at coated pits of plasma membranes as well as in endosomes. These results clearly show that MSR mediates the endocytic uptake and degradation of AGE proteins, suggesting a new role of MSR in biological recognition of AGE in vivo.