Oestrogen receptor alpha is required for biochanin A-induced apolipoprotein A-1 mRNA expression in HepG2 cells.
Epidemiological studies have indicated that soya consumption may produce a better plasma lipid profile. The effect may be attributed to the phyto-oestrogens in soya. The red clover (Trifolium pratense) isoflavone biochanin A has a chemical structure similar to those phyto-oestrogens found in soya beans, and is marketed as a nutraceutical for alleviating postmenopausal symptoms. In the present study we investigated the effect of biochanin A on the mRNA expression of ApoA-1 in the hepatic cell line HepG2. Real-time PCR revealed that biochanin A increased ApoA-1 mRNA abundance in cells expressing oestrogen receptor (ER) alpha. Without ERalpha transfection, biochanin A had no effect on mRNA abundance. In order to study the transcriptional control, a fragment of the 5'-flanking region of the ApoA-1 gene was amplified and inserted in a firefly luciferase reporter plasmid. The reporter assay indicated that the transactivation of the ApoA-1 promoter was induced by biochanin A in HepG2 cells transfected with the ERalpha expression plasmid. This induction was reduced by the anti-oestrogen ICI 182,780, whereas the inhibitors of protein kinase (PK) C, PKA, or mitogen-activated kinase (ERK) had no suppressive effect. The present study illustrated that biochanin A might up regulate hepatic apoA-1 mRNA expression through an ER-dependent pathway.
Chan
Ming Yan
MY
Department of Biochemistry, Faculty of Medicine, The Chinese University of Hong Kong, Room 507C, MMW Bldg, Shatin NT, Hong Kong.
Wai Man
Gho
G
Chen
Zhen-yu
ZY
Wang
Jun
J
Leung
Lai K
LK
D016632:Apolipoprotein A-I / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D019833:Genistein / Q000032:analysis / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology; D008156:Luciferases / Q000037:antagonists & inhibitors; D048789:Phytoestrogens / Q000032:analysis / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014162:Transfection; D014407:Tumor Cells, Cultured
D016632:Apolipoprotein A-I; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007529:Isoflavones; D048789:Phytoestrogens; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019833:Genistein; D008156:Luciferases; C004541:biochanin A