Glucose-regulated protein 78 inhibits scavenger receptor A-mediated internalization of acetylated low density lipoprotein
Glucose-regulated protein 78 inhibits scavenger receptor A-mediated internalization of acetylated low density lipoprotein
复制标题
葡萄糖调节蛋白 78 抑制清道夫受体 A 介导的乙酰化低密度脂蛋白的内化
DOI：
10.1016/j.yjmcc.2009.08.011
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发表时间：
2009-11-01
影响因子：
5
通讯作者：
Chen, Qi
中科院分区：
文献类型：
--
作者：
Ben, Jingjing;Gao, Song;Chen, Qi
A类清道夫受体（SR-A）在泡沫细胞形成中起重要作用。然而，受体-配体复合物的内在化机制仍不清楚。本研究的目的是探讨SR-A介导的巨噬细胞内脂质积聚的分子调控机制。采用拉小丑法（pull-clown assay）鉴定了与SR-A胞浆区（CSR-A）结合的葡萄糖调节蛋白78（GRP 78）。免疫沉淀和人工表达蛋白结合实验证明GRP 78与SR-A在细胞内直接特异结合。间接免疫荧光和western blot分析表明，它们共定位于细胞膜和细胞质中。过表达GRP 78特异性抑制SR-A介导的荧光乙酰化低密度脂蛋白（SR-A的特异性配体）的摄取，而不改变细胞SR-A的表达和结合能力，并显著抑制细胞内胆固醇酯的积累，这可能部分归因于抑制c-Jun-NH 2-末端激酶信号通路。这些结果表明，GRP 78可以作为SR-A介导的修饰的低密度脂蛋白内化到巨噬细胞中的抑制剂（C）2009 Elsevier Inc. All rights reserved.
Class A scavenger receptor (SR-A) plays an important role in foam cell formation. However, the mechanism underlying the internalization of the receptor-ligand complexes remains unclear. The aim of the present study was to investigate the molecular mechanism to regulate SR-A-mediated intracellular lipid accumulation in macrophages A pull-clown assay was performed and glucose-regulated protein 78 (GRP78) was identified to bind with the cytoplasmic domain of SR-A (CSR-A). Immunoprecipitation and artificially expressed protein binding assay demonstrated the direct specific binding of GRP78 with SR-A in cells. Indirect immunofluorescence assay and western blot analysis showed their co-localization in membrane and cytoplasm. Over-expression of GRP78 specifically inhibited SR-A-mediated uptake of fluorescent acetylated low-density lipoprotein, a specific ligand for SR-A, without altering cellular SR-A expression and binding ability, and significantly inhibited cholesterol ester accumulation in cells, which can be partly attributed to the suppression of c-Jun-NH2-terminal kinase signaling pathway. These results suggest that GRP78 may act as an inhibitor of SR-A-mediated internalization of modified low-density lipoprotein into macrophages (C) 2009 Elsevier Inc. All rights reserved.