UDP Glucuronosyltransferase Family 1 Member A3 (UGT1A3) is an enzyme that catalyzes the C24-glucuronidation of the primary bile acid (chenodeoxycholic acid, CDCA) and secondary bile acid (lithocholic acid, LCA). In human hepatoma HepG2 cells, an NR1H2,3 (liver X receptor, LXR) agonist T0901317 induced UGT1A3 expression in a dose- and time-dependent manner (Verreault M et al. 2006). Endogenous NR1H2,3 (LXR) agonists were also investigated by measuring UGT1A3 expression in HepG2 cells treated with 22R-hydroxycholesterol or 24S-hydroxycholesterol. Although the strongest increase in UGT1A3 mRNA levels was reached in the presence of T0901317, 24S-hydroxycholesterol treatment produced a significant induction of UGT1A3 expression, whereas 22R-hydroxycholesterol displayed no significant effects. Furthermore, UGT1A3 gene induction occured through binding of the LXRalpha:RXRalpha heterodimer to a functional LXR response element (LXRE) which was identified in the proximal part of the UGT1A3 promoter gene by site-directed mutagenesis, electrophoretic mobility shift assays and chromatin immunoprecipitation experiments (Verreault M et al. 2006).
Kaeding, J, Verreault, M, Trottier, J, Caron, P, Staels, B, Tukey, RH, Bonzo, JA, Bélanger, J, Barbier, O, Senekeo-Effenberger, K
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