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
Copyright policy )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
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.
- Guangdong Medical College China (People's Republic of)
Time Factors, Dose-Response Relationship, Drug, Transcription, Genetic, Serine Endopeptidases, Down-Regulation, Hep G2 Cells, Diosgenin, Saponins, Lipid Metabolism, MicroRNAs, Cholesterol, Humans, Proprotein Convertases, RNA, Messenger, Proprotein Convertase 9, Sterol Regulatory Element Binding Protein 1, Triglycerides, ATP Binding Cassette Transporter 1, Foam Cells, Sterol Regulatory Element Binding Protein 2
Time Factors, Dose-Response Relationship, Drug, Transcription, Genetic, Serine Endopeptidases, Down-Regulation, Hep G2 Cells, Diosgenin, Saponins, Lipid Metabolism, MicroRNAs, Cholesterol, Humans, Proprotein Convertases, RNA, Messenger, Proprotein Convertase 9, Sterol Regulatory Element Binding Protein 1, Triglycerides, ATP Binding Cassette Transporter 1, Foam Cells, Sterol Regulatory Element Binding Protein 2
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