PMID: 15560369Nov 25, 2004Paper

Stimulation of transcriptional expression of human UDP-glucuronosyltransferase 1A1 by dexamethasone

Molecular Biology Reports
Masanobu KanouTakaharu Mizutani

Abstract

Human UDP-glucuronosyltransferase (UGT) 1A1 is only enzyme in the conjugation of bilirubin for prevention of hyperbilirubinemia and jaundice. Deletion or mutation of the UGT1A1 gene causes Crigler-Najjar syndrome or Gilbert's syndrome. We previously reported the functional promoter region for expression of UGT1A1 [Hepatology Research 9, 152-163 (1997)]. We investigated the influence of some drugs on the transient transfection assay of the luciferase reporter gene containing the 5'-promoter region -3174/+14 of UGT1A1 in HepG2 cells. Among drugs investigated, dexamethasone was the most effective at the range of concentration of 10-100 microM, whereas stimulation by beta-estradiol was not found. We also could not find stimulation by bilirubin of the endogenous main substrate for UGT1A1. Stimulation by dexamethasone was continued for 48 hr. The luciferase reporter gene containing the 5'-region of -97/+14 was induced by dexamethasone but the gene of the 5'-region -53/+14 was not. The region -97/-53 is essential for induction by dexamethasone. This region contains HNF1 element, therefore, we speculated that dexamethasone directly and/or indirectly stimulates UGT1A1 expression through this HNF1 region in the promoter region of UGT1A1....Continue Reading

Citations

Mar 12, 2013·Clinical Pharmacokinetics·Azrin N Abd RahmanChristine E Staatz
Jul 4, 2006·Molecular Biology Reports·Toru UsuiTakaharu Mizutani
Mar 22, 2016·European Journal of Clinical Investigation·Jorien Werumeus BuningRobin P F Dullaart
Oct 14, 2017·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ya-Li NieLi-Rong Zhang
Jan 21, 2006·Pharmacogenetics and Genomics·Jacqueline RamírezStephen C Strom
Dec 31, 2009·Journal of Environmental and Public Health·Takaharu Mizutani
Dec 14, 2012·PloS One·Saskia PreissnerKarlheinz Seeger

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