Genistein Enhances Expression Of Glucuronyltransferase In HepG2 Cell

AIMS: Genistein (Gs) is a sort of phytoestrogen which has varied pharmacological functions. Scientists have found out that it can modulate many drug-metabolizing enzymes through activating nuclear receptor. UDP-Glucuronyltransferase (UGT) is the most important phase II enzymes; it can metabolize many endogenous and exogenous substances. The aims of the study were to investigate the induction of expression of UGT1A, UGT2B and their isoforms in HepG2 cells by Gs and its possible mechanism.METHODS: We set up six experimental groups, they are blank control, positive control and four Gs group (1-10μM). Cells were collected at 12h, 24h and 36h respectively after administration. After extracting total RNA, we assayed the mRNA expression of PPARa, UGT1A and its isoforms UGT1A1 and UGT1A9, UGT2B and its iosform UGT2B4 by semi-quantitative RT-PCR. After extracting microsomal protein, we assayed the protein expression of UGT1A by Western Blot.RESULTS: (1) Between 12-36h after administration of the experimental dosages, Gs can increase UGT1A and UGT2B mRNA expression slightly, there were no significant differences between blank and Gs groups. At 12h after administration, the levels of UGT1A and UGT1A9 mRNA were significantly increased in the Gs groups compared to that in the blank (P<0.05); besides, UGT1A mRNA level correlated with Gs dosages positively(r=0.781, P=0.01). At 24h, PPARa and UGT2B4 mRNA expression were significantly increased in the Gs groups in comparison with the blank. In addiction, PPARa and UGT2B4 mRNA levels correlated with Gs dosages positively between 12-36h respectively. (2) The UGT1A protein band intensity increased significantly treated with Gs for 24 h compared to control cells. (3) PPARa mRNA levels correlated with UGT2B4 mRNA expression positively(r=0.568, P<0.01), while it didn't show up between PPARa mRNA and UGT1A9 mRNA.CONCLUTION: (1) 1-10μM Gs can induce the expression of PPARa, UGT2B4, UGT1A and its isoform UGT1A9 significantly. These changes are accompanied by an increase of UGT1A protein expression. (2) PPARa may be an important factor which involved in the UGT2B4 regulation by Gs, that's to say maybe Gs induce expression of UGT by activating PPARa. While, PPARa plays a less important role in the UGT1A9 induction, it indicates that other factors participate in the process.