Genistein and daidzein induced apoA-1 transactivation in hepG2 cells expressing oestrogen receptor-alpha.
Studies have shown that soya consumption has been associated with low incidence of CVD. Because the chemical structures of soya isoflavones are similar to oestrogen, the beneficial outcome may be attributed to the oestrogenicity of these compounds. In this study, effect of the soya isoflavone genistein on the mRNA expression of apoA-1 in the human hepatoma HepG2 cell was investigated. Without oestrogen receptor (ER) alpha transfection, soya isoflavones in the physiological range had no effect on the apoA-1 transcription. Once ERalpha was ectopically expressed in these cells, soya isoflavone dramatically increased the apoA-1 mRNA abundance quantified by real-time PCR. ApoA-1-reporter assays with plasmid constructed from the 5'-flanking segment upstream to the coding region revealed that the transactivation of the apoA-1 promoter was induced by the soya isoflavone in HepG2 cells expressing ERalpha. This induction was reduced by the anti-oestrogen ICI 182780, but not the inhibitors of protein kinase (PK) C, PKA, or mitogen-activated PK. Based on the previously identified response elements on the promoter, a series of truncated promoter reporter plasmids were then constructed. An induction profile of genistein was built and insulin response core element at -411 to -404 appeared to be a potential site of interaction. This study illustrated that soya isoflavones at physiological concentrations could up regulate apoA-1 mRNA expression in ERalpha-transfected HepG2 cells.
Yuen
Yee M
YM
Department of Biochemistry, Faculty of Science, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Leung
Lai K
LK
D016632:Apolipoprotein A-I / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism* / Q000502:physiology; D000077267:Fulvestrant; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D048789:Phytoestrogens / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects
D016632:Apolipoprotein A-I; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D007529:Isoflavones; D048789:Phytoestrogens; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D000077267:Fulvestrant; D004958:Estradiol; C004742:daidzein; D019833:Genistein