JBC INTERFERin siRNA transfection reagent

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M005930200 on January 24, 2001

J. Biol. Chem., Vol. 276, Issue 16, 12822-12826, April 20, 2001
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
276/16/12822    most recent
M005930200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Smirlis, D.
Right arrow Articles by Shephard, E. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Smirlis, D.
Right arrow Articles by Shephard, E. A.

Orphan Receptor Promiscuity in the Induction of Cytochromes P450 by Xenobiotics*

Despina SmirlisDagger §, Roongsiri MuangmoonchaiDagger , Mina EdwardsDagger , Ian R. Phillips||**, and Elizabeth A. ShephardDagger Dagger Dagger

From the Dagger  Department of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, United Kingdom and the || School of Biological Sciences, Queen Mary, University of London, Mile End Road, London E1 4NS, United Kingdom

The mechanisms by which different classes of chemicals induce the same cytochrome P450 (CYP) or the same chemical differentially induces more than one CYP are not well understood. We show that in primary hepatocytes and in vivo in liver (transfected by particle-mediated delivery) two orphan nuclear receptors, constitutive androstane receptor and pregnane X receptor (PXR1), transactivate a CYP gene via the same response element in a xenobiotic-specific manner. The constitutive androstane receptor mediates the barbiturate activation of expression of CYP2B1 and CYP3A1. PXR1 activates both genes in response to synthetic steroids. To exert their effect the receptors bind to the same direct repeat site (DR4) within the phenobarbital response element of the CYP2B1 promoter and to the same DR3 site in the pregnane X response element of CYP3A1. The receptors are therefore promiscuous with respect to DNA binding but not ligand binding. Differences in enhancer half-site spacing may influence the efficiency of interactions between the receptor and the transcription machinery and hence form the basis for the differential induction of CYP2B1 and CYP3A1 in response to barbiturates and synthetic steroids.

* This work was supported by Grant 042495 from the Wellcome Trust.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Recipient of a Wellcome Trust Toxicology Prize studentship.

Recipient of a scholarship from the Royal Thai Government. Present address: Dept. of Clinical Chemistry, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand 50200.

Dagger Dagger To whom correspondence may be addressed: Dept. of Biochemistry and Molecular Biology, University College London, Gower Street, London WC1E 6BT, UK. Tel.: +44-20-7679-2321; Fax: +44-20-7679-7193; E-mail: e.shephard@ucl.ac.uk.

** To whom correspondence may also be addressed: School of Biological Sciences, Queen Mary, University of London, Mile End Rd., London E1 4NS, UK. Tel.: +44-20-7882-6338; Fax: +44-20-8983-0531; E-mail: I.R.Phillips@qmw.ac.uk.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
S. R. Faucette, T. Sueyoshi, C. M. Smith, M. Negishi, E. L. LeCluyse, and H. Wang
Differential Regulation of Hepatic CYP2B6 and CYP3A4 Genes by Constitutive Androstane Receptor but Not Pregnane X Receptor
J. Pharmacol. Exp. Ther., June 1, 2006; 317(3): 1200 - 1209.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
S. Kodama, C. Koike, M. Negishi, and Y. Yamamoto
Nuclear Receptors CAR and PXR Cross Talk with FOXO1 To Regulate Genes That Encode Drug-Metabolizing and Gluconeogenic Enzymes
Mol. Cell. Biol., September 15, 2004; 24(18): 7931 - 7940.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
D. Bauer, N. Wolfram, G. F. Kahl, and K. I. Hirsch-Ernst
Transcriptional Regulation of CYP2B1 Induction in Primary Rat Hepatocyte Cultures: Repression by Epidermal Growth Factor Is Mediated via a Distal Enhancer Region
Mol. Pharmacol., January 1, 2004; 65(1): 172 - 180.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
C. Handschin and U. A. Meyer
Induction of Drug Metabolism: The Role of Nuclear Receptors
Pharmacol. Rev., December 1, 2003; 55(4): 649 - 673.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. Kim, S. Xie, S.-D. Yeh, Y.-F. Lee, L. L. Collins, Y.-C. Hu, C.-R. Shyr, X.-M. Mu, N.-C. Liu, Y.-T. Chen, et al.
Disruption of TR4 Orphan Nuclear Receptor Reduces the Expression of Liver Apolipoprotein E/C-I/C-II Gene Cluster
J. Biol. Chem., November 21, 2003; 278(47): 46919 - 46926.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
J. M. Maglich, D. J. Parks, L. B. Moore, J. L. Collins, B. Goodwin, A. N. Billin, C. A. Stoltz, S. A. Kliewer, M. H. Lambert, T. M. Willson, et al.
Identification of a Novel Human Constitutive Androstane Receptor (CAR) Agonist and Its Use in the Identification of CAR Target Genes
J. Biol. Chem., May 2, 2003; 278(19): 17277 - 17283.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
J. L. Staudinger, A. Madan, K. M. Carol, and A. Parkinson
Regulation of Drug Transporter Gene Expression by Nuclear Receptors
Drug Metab. Dispos., May 1, 2003; 31(5): 523 - 527.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
A. Madan, R. A. Graham, K. M. Carroll, D. R. Mudra, L. A. Burton, L. A. Krueger, A. D. Downey, M. Czerwinski, J. Forster, M. D. Ribadeneira, et al.
Effects of Prototypical Microsomal Enzyme Inducers on Cytochrome P450 Expression in Cultured Human Hepatocytes
Drug Metab. Dispos., April 1, 2003; 31(4): 421 - 431.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
B. Goodwin, K. C. Gauthier, M. Umetani, M. A. Watson, M. I. Lochansky, J. L. Collins, E. Leitersdorf, D. J. Mangelsdorf, S. A. Kliewer, and J. J. Repa
Identification of bile acid precursors as endogenous ligands for the nuclear xenobiotic pregnane X receptor
PNAS, January 7, 2003; 100(1): 223 - 228.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
S. A. Kliewer, B. Goodwin, and T. M. Willson
The Nuclear Pregnane X Receptor: A Key Regulator of Xenobiotic Metabolism
Endocr. Rev., October 1, 2002; 23(5): 687 - 702.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
L. Xiao, X. Cui, V. Madison, R. E. White, and K.-C. Cheng
Insights from a Three-Dimensional Model into Ligand Binding to Constitutive Active Receptor
Drug Metab. Dispos., September 1, 2002; 30(9): 951 - 956.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. M. Maglich, C. M. Stoltz, B. Goodwin, D. Hawkins-Brown, J. T. Moore, and S. A. Kliewer
Nuclear Pregnane X Receptor and Constitutive Androstane Receptor Regulate Overlapping but Distinct Sets of Genes Involved in Xenobiotic Detoxification
Mol. Pharmacol., September 1, 2002; 62(3): 638 - 646.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
J. Makinen, C. Frank, J. Jyrkkarinne, J. Gynther, C. Carlberg, and P. Honkakoski
Modulation of Mouse and Human Phenobarbital-Responsive Enhancer Module by Nuclear Receptors
Mol. Pharmacol., August 1, 2002; 62(2): 366 - 378.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
A. Ueda, H. K. Hamadeh, H. K. Webb, Y. Yamamoto, T. Sueyoshi, C. A. Afshari, J. M. Lehmann, and M. Negishi
Diverse Roles of the Nuclear Orphan Receptor CAR in Regulating Hepatic Genes in Response to Phenobarbital
Mol. Pharmacol., January 1, 2002; 61(1): 1 - 6.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
B. Goodwin, L. B. Moore, C. M. Stoltz, D. D. McKee, and S. A. Kliewer
Regulation of the Human CYP2B6 Gene by the Nuclear Pregnane X Receptor
Mol. Pharmacol., September 1, 2001; 60(3): 427 - 431.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. R. Kast, B. Goodwin, P. T. Tarr, S. A. Jones, A. M. Anisfeld, C. M. Stoltz, P. Tontonoz, S. Kliewer, T. M. Willson, and P. A. Edwards
Regulation of Multidrug Resistance-associated Protein 2 (ABCC2) by the Nuclear Receptors Pregnane X Receptor, Farnesoid X-activated Receptor, and Constitutive Androstane Receptor
J. Biol. Chem., January 18, 2002; 277(4): 2908 - 2915.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2001 by the American Society for Biochemistry and Molecular Biology.