title: [Endoplasmic reticulum stress mediates oxidized low density lipoprotein-induced scavenger receptor A1 upregulation in macrophages].
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.
authors.affiliation: 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@126.com.
authors.forename: Shu-Tong
authors.initials: ST
authors.lastname: Yao
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Cheng
authors.initials: C
authors.lastname: Miao
authors.forename: Hua
authors.initials: H
authors.lastname: Tian
authors.forename: Na-Na
authors.initials: NN
authors.lastname: Yang
authors.forename: Shou-Dong
authors.initials: SD
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Zhai
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Yi-Wei
authors.initials: YW
authors.lastname: Wang
authors.forename: Shu-Cun
authors.initials: SC
authors.lastname: Qin
mesh_terms: D000818:Animals; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D006360:Heat-Shock Proteins / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D051117:Scavenger Receptors, Class A / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D008077:Lipoproteins, LDL; D051117:Scavenger Receptors, Class A; C099252:oxidized low density lipoprotein; D002784:Cholesterol