The role of Ah receptor in induction of human UDP-glucuronosyltransferase 1A1.
UDP-glucuronosyltransferases (UGTs) catalyze a major metabolic pathway initiating the transfer of glucuronic acid from uridine 5'-diphosphoglucuronic acid to endogenous and exogenous substances. Endogenous substances include bile acids, steroids, phenolic neurotransmitters, and bilirubin. Xenobiotic substances include dietary substances, therapeutics, and environmental compounds. The versatility in the selection of substrates for glucuronidation results from the multiplicity of the UGTs in addition to the ability of these genes to be regulated. UDP-glucuronosyltransferase 1A1 (UGT1A1), responsible for the glucuronidation of bilirubin, is controlled in a tissue-specific manner and can be regulated following environmental exposure. This chapter describes materials and methods for the examination of molecular interactions that control UGT1A1 expression and induction in response to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Using an in vitro cell culture system, we mapped a regulatory sequence that contains a xenobiotic response element core sequence in the enhancer region of the UGT1A1 gene. Similar to regulation of CYP1A1, the transcriptional activation of UGT1A1 by TCDD is mediated through the aryl hydrocarbon receptor.
Yueh
Mei-Fei
MF
Department of Pharmacology, Chemistry & Biochemistry, Laboratory of Environmental Toxicology, University of California, San Diego, La Jolla, USA.
Bonzo
Jessica A
JA
Tukey
Robert H
RH
D015153:Blotting, Western; D045744:Cell Line, Tumor; D004742:Enhancer Elements, Genetic; D004790:Enzyme Induction / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D014453:Glucuronosyltransferase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D011401:Promoter Regions, Genetic; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D013723:Teratogens / Q000633:toxicity; D015533:Transcriptional Activation; D000099148:UGT1A1 Enzyme
D014453:Glucuronosyltransferase; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D013723:Teratogens; D000099148:UGT1A1 Enzyme