Glucose-regulated protein 78 inhibits scavenger receptor A-mediated internalization of acetylated low density lipoprotein
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- 作者：Jingjing Ben ; Song Gao ; Xudong Zhu ; Yuan Zheng ; Yan Zhuang ; Hui Bai ; Yong Xu ; Yong Ji ; Jiahao Sha ; Zhigang He ; Qi Chen
- 关键词：Class A scavenger receptor ; Macrophages ; Foam cell formation ; Glucose-regulated protein 78 ; Internalization of acetylated LDL ; 6-Aminonicotinamide ; Fluvastatin ; JNK signaling pathway
- 刊名：Journal of Molecular and Cellular Cardiology
- 出版年：2009
- 出版时间：November 2009
- 年：2009
- 卷：47
- 期：5
- 页码：646-655
- 全文大小：699 K
文摘
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-down 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.