A novel compound 4010B-30 upregulates apolipoprotein A-I gene expression through activation of PPARγ in HepG2 cells

Atherosclerosis
Yu DuBin Hong

Abstract

Apolipoprotein (Apo) A-I is the major lipoprotein content of HDL and upregulating endogenous ApoA-I expression has been proposed as a desirable approach to raise the functional HDL. In this study we investigated the effect of a novel small molecule 4010B-30 on transcriptional regulation of ApoA-I gene in HepG2 cells, and the influence on the level of ApoA-I expression and function. Then the mechanisms by which 4010B-30 regulated ApoA-I expression was further explored. In human hepatic HepG2 cells, 4010B-30 increased the mRNA level and the protein production of ApoA-I both in cell lysates and media. The 4010B-30-induced ApoA-I containing particles increased cholesterol efflux from RAW264.7 macrophages. 4010B-30 also upregulated ABCA1 expression confirmed by transcriptional activity assay and Western blot analysis in both HepG2 and RAW264.7 cells. Promoter luciferase assay was used to identify the 4010B-30-responsive region which is mapped to the proximal -277bp region of the ApoA-I promoter. Further study indicated that the regulation of 4010B-30 on ApoA-I transcription or protein expression in HepG2 cells was abrogated with the suppression of PPARγ by its small interfering RNA or a specific inhibitor, GW9662. These findings sug...Continue Reading

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Citations

May 30, 2015·Expert Opinion on Drug Discovery·Yu DuBin Hong
Jan 28, 2016·Journal of Cellular Biochemistry·Vladimir S ShavvaSergey V Orlov
Dec 1, 2019·International Journal of Molecular Sciences·Jehad Z TayyebJogchum Plat

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