Characterization of the Isoflavone Pratensein as a Novel Transcriptional Up-Regulator of Scavenger Receptor Class B Type I in HepG2 Cells

概要

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Scavenger receptor class B type I (SR-BI), as well as its human homologue CLA-1, plays an important role in reverse cholesterol transport (RCT) as high density lipoprotein (HDL) receptor. Using a previously developed cell-based screening model for CLA-1 up-regulators, pratensein, was shown to present activity in elevating CLA-1 transcriptional level. In this study, three other isoflavones including formononetin, genistein and daidzein were also shown to up-regulate CLA-1 transcriptional activity in the cell-based reporter assay. The effects of pratensein on up-regulating CLA-1 expression were demonstrated at both mRNA and protein levels, and validated by its increasing of 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate-labeled (DiI)-HDL uptake in HepG2 cells. Furthermore, the cis-elements responsible for the pratensein up-regulatory effects were mapped to the −1055/−182 bp fragment of CLA-1 promoter in HepG2 cells. These findings might provide a new molecular mechanism by which isoflavones potentially prevent atherosclerosis.