Characterization of the isoflavone pratensein as a novel transcriptional up-regulator of scavenger receptor class B type I in HepG2 cells.
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.
Yang
Yuan
Y
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College.
Jiang
Wei
W
Wang
Li
L
Zhang
Zhong-Bing
ZB
Si
Shu-Yi
SY
Hong
Bin
B
D000190:Actinomyces / Q000737:chemistry; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D017930:Genes, Reporter; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008156:Luciferases / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis* / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects*; D015854:Up-Regulation
D007529:Isoflavones; D008075:Lipoproteins, HDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; C543998:4'-methoxy-3',5,7-trihydroxyisoflavone; D008156:Luciferases