Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 47, Issue 5, Pages 646-655Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2009.08.011
Keywords
Class A scavenger receptor; Macrophages; Foam cell formation; Glucose-regulated protein 78; Internalization of acetylated LDL; 6-Aminonicotinamide; Fluvastann; JNK signaling pathway
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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.
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