MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Metz, R. P.
Right arrow Articles by Ritter, J. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Metz, R. P.
Right arrow Articles by Ritter, J. K.

Vol. 58, Issue 2, 319-327, August 2000

Involvement of Hepatocyte Nuclear Factor 1 in the Regulation of the UDP-Glucuronosyltransferase 1A7 (UGT1A7) Gene in Rat Hepatocytes1

Richard P. Metz, Diana J. Auyeung, Fay K. Kessler, and Joseph K. Ritter

Department of Pharmacology and Toxicology, Virginia Commonwealth University, Medical College of Virginia, Richmond, Virginia

UDP-glucuronosyltransferase 1A7 (UGT1A7) is a major UGT contributing to the glucuronidation of xenobiotic phenols in rats. Its expression in rat liver is tightly regulated, with low constitutive and high inducible expression in response to aryl hydrocarbon receptor ligands and oltipraz. Previously, we reported the absence of 3-methylcholanthrene- or oltipraz-responsive elements in the 1.6-kbp region flanking the UGT1A7 promoter. However, potential binding sites were noted for several liver-enriched transcription factors. Here we show that deletion of the hepatic nuclear factor (HNF)3, HNF4, and CCAAT-enhancer binding protein-like binding sites had no effect on the expression of a UGT1A7 reporter plasmid, p(-965/+56)1A7-Luc, in primary rat hepatocytes. The full activity of the promoter was contained in the region between bases -157 and +76. Two sites of binding by rat liver nuclear proteins were detected in this region by DNase footprinting. PR-1 corresponded to the HNF1-like binding site between bases -52 and -38, whereas PR-2 was located between -30 to -6. Gel retardation studies supported the presence of HNF1alpha in the PR-1 DNA-liver nuclear protein complex. Mutation of PR-1 inhibited binding in the gel shift assay, prevented activation by overexpressed HNF1 in human embryonic kidney cells, and reduced by >80% the maximal luciferase activities expressed from basal and 3-methylcholanthrene-responsive UGT1A7 gene reporter constructs in primary rat hepatocytes. These data provide evidence for an important stimulatory role of HNF1 in promoting UGT1A7 gene expression in rat liver.

1 This work was supported by Grant R29-ES07762 from the National Institute of Environmental Health Sciences. R.M. and D.A. were supported by National Institute of Environmental Health Sciences Training Grant ES07087.

Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 EndocrinologyHome page
Y. Emi, S.-i. Ikushiro, and Y. Kato
Thyroxine-Metabolizing Rat Uridine Diphosphate-Glucuronosyltransferase 1A7 Is Regulated by Thyroid Hormone Receptor
Endocrinology, December 1, 2007; 148(12): 6124 - 6133.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
O. Barbier, H. Girard, Y. Inoue, H. Duez, L. Villeneuve, A. Kamiya, J.-C. Fruchart, C. Guillemette, F. J. Gonzalez, and B. Staels
Hepatic Expression of the UGT1A9 Gene Is Governed by Hepatocyte Nuclear Factor 4{alpha}
Mol. Pharmacol., January 1, 2005; 67(1): 241 - 249.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
P. A. Gregory, R. H. Lewinsky, D. A. Gardner-Stephen, and P. I. Mackenzie
Coordinate Regulation of the Human UDP-Glucuronosyltransferase 1A8, 1A9, and 1A10 Genes by Hepatocyte Nuclear Factor 1{alpha} and the Caudal-Related Homeodomain Protein 2
Mol. Pharmacol., April 1, 2004; 65(4): 953 - 963.
[Abstract] [Full Text]

Home page
 Drug Metab. Dispos.Home page
K. Toide, Y. Takahashi, H. Yamazaki, Y. Terauchi, T. Fujii, A. Parkinson, and T. Kamataki
Hepatocyte Nuclear Factor-1alpha Is a Causal Factor Responsible for Interindividual Differences in the Expression of UDP-Glucuronosyltransferase 2B7 mRNA in Human Livers
Drug Metab. Dispos., June 1, 2002; 30(6): 613 - 615.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
N. R. Vansell and C. D. Klaassen
Increase in Rat Liver UDP-Glucuronosyltransferase mRNA by Microsomal Enzyme Inducers that Enhance Thyroid Hormone Glucuronidation
Drug Metab. Dispos., March 1, 2002; 30(3): 240 - 246.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
Z. Luo and R. N. Hines
Regulation of Flavin-Containing Monooxygenase 1 Expression by Ying Yang 1 and Hepatic Nuclear Factors 1 and 4
Mol. Pharmacol., December 1, 2001; 60(6): 1421 - 1430.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
R. N. Hines, Z. Luo, T. Cresteil, X. Ding, R. A. Prough, J. L. Fitzpatrick, S. L. Ripp, K. C. Falkner, N.-L. Ge, A. Levine, et al.
Molecular Regulation of Genes Encoding Xenobiotic-Metabolizing Enzymes: Mechanisms Involving Endogenous Factors
Drug Metab. Dispos., April 13, 2001; 29(5): 623 - 633.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
R. A. Memon, A. H. Moser, J. K. Shigenaga, C. Grunfeld, and K. R. Feingold
In Vivo and in Vitro Regulation of Sterol 27-Hydroxylase in the Liver during the Acute Phase Response. POTENTIAL ROLE OF HEPATOCYTE NUCLEAR FACTOR-1
J. Biol. Chem., August 3, 2001; 276(32): 30118 - 30126.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2000 by the American Society for Pharmacology and Experimental Therapeutics