Oestrogen receptor α is required for biochanin A-induced apolipoprotein A-1 mRNA expression in HepG2 cells

Abstract

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) a. Without ERa transfection, biochanin A had no effect on mRNA abundance. In order to study the transcriptional control, a fragment of the 5 0 -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 ERa 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.Biochanin A: Oestrogen receptors: Apolipoprotein A-1: Liver cancer cells CVD comprises the major cause of death in Western countries. Recent projections suggest that CVD will be the leading cause of death in both developed and developing regions of the world by the year 2020 1 . Epidemiological studies have associated the consumption of isoflavonoids with a lower incidence of CVD 2 . In normal postmenopausal women, consuming whole soya foods with 60 mg isoflavones per d may help to alleviate several key clinical risk factors for CVD 3 .

A Comparative Analysis of Genistein and Daidzein in Affecting Lipid Metabolism in Rat Liver

“…In fact, genistein has been previously demonstrated to be stronger than daidzein in increasing the gene expression of apolipoprotein A-I, a major component of high density lipoprotein, in HepG2 cells [ 20 ]. As the gene expression of apolipoprotein A-I is under the control of estrogen receptor-alpha [ 21 ], this effect is ascribable to the difference between these isoflavones in affinity for this receptor. Also, it has been reported that genistein interferes with the activation of CCAAT/enhancer-binding protein (C/EBP)β by inhibiting tyrosine-phosphorylation [ 22 ].…”