Methyl protodioscin increases ABCA1 expression and cholesterol efflux while inhibiting gene expressions for synthesis of cholesterol and triglycerides by suppressing SREBP transcription and microRNA 33a/b levels

Methyl protodioscin increases ABCA1 expression and cholesterol efflux while inhibiting gene expressions for synthesis of cholesterol and triglycerides by suppressing SREBP transcription and microRNA 33a/b levels
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甲基原薯蓣皂苷可增加 ABCA1 表达和胆固醇流出,同时通过抑制 SREBP 转录和 microRNA 33a/b 水平来抑制胆固醇和甘油三酯合成的基因表达

DOI:
10.1016/j.atherosclerosis.2015.02.034
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发表时间:
2015-04-01
期刊:
影响因子:
5.3
通讯作者:
Lin, Guorong
Lin, Guorong
中科院分区:
医学2区
文献类型:
--
作者:
Ma, Weilie;Ding, Hang;Lin, Guorong

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Sterol regulatory element-binding proteins (SREBPs) regulate homeostasis of LDL, HDL and triglycerides. This study was aimed to determine if inhibition of SREBPs by methyl protodioscin (MPD) regulates downstream gene and protein expressions of lipid metabolisms. In THP-1 macrophages, MPD increases levels of ABCA1 mRNA and protein in dose-and time-dependent manners, and apoA-1-mediated cholesterol efflux. The underlying mechanisms for the effects is that MPD inhibits the transcription of SREBP1c and SREBP2, and decreases levels of microRNA 33a/b hosted in the introns of SREBPs, which leads to reciprocally increase ABCA1 levels. In HepG2 cells, MPD shows the same effects as these observed in THP-1 macrophages. MPD also decreases the gene expressions of HMGCR, FAS and ACC for cholesterol and fatty acid synthesis. MPD further promotes LDL receptor through reducing the PCSK9 level. Collectively, the study demonstrates that MPD potentially increase HDL cholesterol while reducing LDL cholesterol and triglycerides. (C) 2015 Elsevier Ireland Ltd. All rights reserved.