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[Endoplasmic reticulum stress mediates oxidized low density lipoprotein-induced scavenger receptor A1 upregulation in macrophages.] [Article in Chinese]

YAO Shu-Tong, ZHAO Li, MIAO Cheng, TIAN Hua, YANG Na-Na , GUO Shou-Dong, ZHAI Lei, Chen Jun, WANG Yi-Wei, QIN Shu-Cun

Institute of Atherosclerosis, Key Laboratory of Atherosclerosis in Universities of Shandong； College of Basic Medical Sciences, Taishan Medical University, Tai'an 271000, China； Affiliated Hospital of Chengde Medical University, Chengde 067000, China

Abstract

The present study was to investigate whether endoplasmic reticulum stress (ERS) was involved in oxidized low density
lipoprotein (ox-LDL)-induced scavenger receptor A1 (SR-A1) upregulation in macrophages. RAW264.7 cells were pretreated with 20 mmol/L of 4-phenylbutyric acid (PBA) for 30 min and then treated with ox-LDL (50 mg/L) for 12 h or stimulated with 2 mg/L tunicamycin (TM) or 2 μmol/L thapsigagin (TG) for 4 h. In addition, RAW264.7 cells were incubated with 0.5, 1 and 2 mg/L TM for 4 h or treated with 2 mg/L TM for 1, 2 and 4 h, respectively. The intracellular total cholesterol (TC) content was measured using a tissue/cell total cholesterol assay kit. The protein and mRNA expressions of SR-A1 and glucose-regulated protein 78 (GRP78) were analyzed by Western blot and real-time PCR, respectively. Dil-ox-LDL uptake was detected using a microplate reader. The results showed that ox-LDL-induced cholesterol accumulation in macrophages was attenuated by PBA, an ERS inhibitor. Ox-LDL caused significant SR-A1 upregulation with concomitant activation of ERS as assessed by upregulation of GRP78, whereas PBA significantly inhibited the ox-LDL-induced SR-A1 upregulation (P < 0.05) and slightly decreased GRP78 expression by 39.3% (P = 0.057). TM, an ERS inducer, upregulated SR-A1 protein expression and ox-LDL uptake in dose- and time-dependent manner, but had no significant effect on SR-A1 mRNA level. However, the TM- or TG-induced SR-A1 upregulation and ox-LDL uptake were significantly mitigated by PBA. These data indicate that ERS plays a critical role in ox-LDL-induced SR-A1 upregulation, which in turn enhances the foam cell formation by uptaking more ox-LDL.

Key words: endoplasmic reticulum stress; oxidized low density lipoprotein; Macrophage; scavenger receptor A1

Received: 2014-01-05　　Accepted: 2014-02-10

Corresponding author: 王义围,秦树存　　E-mail: shucunqin@hotmail.com,chengdewyw@126.com

Citing This Article：

YAO Shu-Tong, ZHAO Li, MIAO Cheng, TIAN Hua, YANG Na-Na , GUO Shou-Dong, ZHAI Lei, Chen Jun, WANG Yi-Wei, QIN Shu-Cun. [Endoplasmic reticulum stress mediates oxidized low density lipoprotein-induced scavenger receptor A1 upregulation in macrophages.] [Article in Chinese]. Acta Physiol Sin 2014; 66 (5): 612-618 (in Chinese with English abstract).