Endoplasmic reticulum stress mediates oxidized low density lipoprotein-induced scavenger receptor A1 upregulation in macrophages.
- Author:
Shu-Tong YAO
1
,
2
;
2
,
3
;
Li ZHAO
;
Cheng MIAO
;
Hua TIAN
;
Na-Na YANG
;
Shou-Dong GUO
;
Lei ZHAI
;
Jun CHEN
;
Yi-Wei WANG
;
Shu-Cun QIN
Author Information
1. 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. shucunqin@hotmail.com; chengdewyw@
2. com.
3. ;chengdewyw@
- Publication Type:Journal Article
- MeSH:
Animals;
Cell Line;
Cholesterol;
metabolism;
Endoplasmic Reticulum Stress;
Heat-Shock Proteins;
metabolism;
Lipoproteins, LDL;
pharmacology;
Macrophages;
drug effects;
metabolism;
Mice;
Scavenger Receptors, Class A;
metabolism;
Up-Regulation
- From:
Acta Physiologica Sinica
2014;66(5):612-618
- CountryChina
- Language:Chinese
-
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.
