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Oxidized low density lipoprotein induces macrophage endoplasmic reticulum stress via CD36

YAO Shu-Tong, SANG Hui, YANG Na Na, KANG Li, TIAN Hua, ZHANG Ying, SONG Guo-Hua , QIN Shu-Cun

Institute of Atherosclerosis； Institute of Preclinical Medicine, Taishan Medical College, Taian 271000, China

Abstract

The purpose of the present study is to explore the effect of oxidized low density lipoprotein (ox-LDL) on the induction ofendoplasmic reticulum stress (ERS) and the underlying mechanisms in ox-LDL-induced macrophage foam-forming process. RAW264.7macrophages were cultured in DMEM medium containing 10% fetal bovine serum, and then treated with ox-LDL (25, 50 and 100 mg/L),anti-CD36 monoclonal antibody+ox-LDL and tunicamycin (TM), respectively. After incubation for 24 h, the cells were collected. Thecellular lipid accumulation was showed by oil red O staining and the content of cellular total cholesterol was quantified by enzymaticcolorimetry. The expression of glucose-regulated protein 94 (GRP94), a molecular marker of ERS, was determined by immunocytochemistryassay. The levels of GRP94 protein, phosphorylated inositol-requiring enzyme 1 (p-IRE1) and X box binding protein1 (XBP1) in RAW264.7 cells were detected by Western blotting. The results indicated that after incubation with ox-LDL (25, 50 and100 mg/L) for 24 h, a large amount of lipid droplets were found in the cytoplasm, and the contents of cellular total cholesterol wereincreased by 2.1, 2.8 and 3.1 folds compared with the control, respectively. Anti-CD36 antibody decreased markedly the cellular lipidaccumulation induced by ox-LDL at 100 mg/L. Both ox-LDL and TM, a specific ERS inducer, could up-regulate the protein expressionof GRP94 in a dose-dependent manner. Furthermore, p-IRE1 and XBP1, two key components of the unfolded protein response, were also significantly induced by the treatment with ox-LDL. The up-regulations of the three proteins induced by ox-LDL were inhibitedsignificantly when the macrophages were pre-incubated with anti-CD36 antibody. These results suggest that ox-LDL may induce ERSin a dose-dependent way and subsequently activate the unfolded protein response signaling pathway in RAW264.7 macrophages,which is potentially mediated by scavenger receptor CD36.

Key words: endoplasmic reticulum stress; Macrophage; oxidized low density lipoprotein; CD36; atherosclerosis

Received: 2010-06-17　　Accepted: 2010-07-26

Corresponding author: 秦树存　　E-mail: shucunqin@hotmail.com

Citing This Article：

YAO Shu-Tong, SANG Hui, YANG Na Na, KANG Li, TIAN Hua, ZHANG Ying, SONG Guo-Hua , QIN Shu-Cun. Oxidized low density lipoprotein induces macrophage endoplasmic reticulum stress via CD36. Acta Physiol Sin 2010; 62 (5): 433-440 (in Chinese with English abstract).