Inhibitory effect of apolipoprotein A-I mimetic peptide D-4 F on scavenger receptor A1 in macrophage-derived foam cells
10.3969/j.issn.1000-4718.2014.10.003
- VernacularTitle:载脂蛋白 A-I 模拟肽 D-4F 对巨噬细胞源性泡沫细胞清道夫受体 A1的抑制作用
- Author:
Li ZHAO
;
Shutong YAO
;
Jun CHEN
;
Cheng MIAO
;
Yanyan LI
;
Hua TIAN
;
Jian ZHOU
;
Lei ZHAI
;
Hui SANG
;
Yiwei WANG
;
Shucun QIN
- Publication Type:Journal Article
- Keywords:
Atherosclerosis;
Apolipoprotein A-I mimetic peptide;
Endoplasmic reticulum stress;
Scavenger receptor A1;
Foam cells
- From:
Chinese Journal of Pathophysiology
2014;(10):1742-1747
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the inhibitory effect of apolipoprotein A-I mimetic peptide D-4F on the scaven-ger receptor A1 ( SR-A1 ) in macrophage-derived foam cells induced by oxidized low-density lipoprotein ( ox-LDL ) . METHODS:RAW264.7 cells were pretreated with different concentrations (12.5, 25 and 50 mg/L) of D-4F or 50 mg/L inactive control peptide scrambled D-4F (sD-4F) for 1 h or endoplasmic reticulum stress (ERS) inhibitor 4-phenylbutyr-ic acid (5 mmol/L) for 30 min, followed by the treatment with 100 mg/L ox-LDL for 12 h.In addition, the cells were pre-treated with 50 mg/L D-4F or sD-4F for 1 h, and then stimulated with 2 mg/L tunicamycin (TM;an ERS inducer), for 4 h.The viability of the cells was measured by MTT assay, and the content of intracellular total cholesterol ( TC) was meas-ured by a tissue/cell TC assay.The protein and mRNA levels of SR-A1 and glucose-regulated protein 78 (GRP78) were analyzed by Western blotting and quantitative real-time PCR, respectively.The fluorescence intensity of DiI-ox-LDL in the cells was detected by a multifunctional microplate reader.RESULTS:D-4F significantly reduced ox-LDL-induced macro-phage injury and intracellular cholesterol accumulation, and attenuated the ox-LDL-induced expression of SRA1 and GRP78 in a dose-dependent manner.Additionally, D-4F significantly inhibited the TM-induced protein expression of SR-A1 and GRP78, and attenuated the uptake of ox-LDL by macrophages.CONCLUSION: D-4F reduces ox-LDL-induced macro-phage cholesterol accumulation and injury by inhibiting SR-A1 expression.The mechanism may be related to the inhibition of ERS signaling pathway mediated by GRP78.
