Skip Navigation


ToxSci Advance Access originally published online on September 22, 2006
Toxicological Sciences 2006 94(2):379-387; doi:10.1093/toxsci/kfl116
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
94/2/379    most recent
kfl116v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Guzelian, J.
Right arrow Articles by Guzelian, P. S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Guzelian, J.
Right arrow Articles by Guzelian, P. S.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2006. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Identification of Genes Controlled by the Pregnane X Receptor by Microarray Analysis of mRNAs from Pregnenolone 16{alpha}-Carbonitrile–Treated Rats

Jeffrey Guzelian*, Joyce L. Barwick{dagger}, Lawrence Hunter{ddagger}, Tzu L. Phang{ddagger}, Linda C. Quattrochi{dagger},1 and Philip S. Guzelian{dagger}

* Department of Medicine, University of Colorado, Boulder, Colorado 80262 {dagger} Section of Medical Toxicology, School of Medicine, Denver, Colorado 80262 {ddagger} Center for Computational Pharmacology, University of Colorado at Denver and Health Sciences Center, Denver, Colorado 80262

Received May 31, 2006; accepted August 2, 2006

Mammalian liver contains a pregnane X receptor (PXR, NR1I2), which binds drugs and other xenobiotics, and stimulates (or suppresses) expression of numerous genes involved in the metabolic elimination of foreign compounds and some toxic endogenous substances. In the present study, we used microarray analysis to identify genes whose expression in rat liver was significantly altered by pregnenolone 16{alpha}-carbonitrile (PCN) treatment. PCN is a synthetic steroid that induces cytochrome P4503A expression and is hepatoprotective by increasing resistance to subsequent stressful insults. Significant induction was seen for 138 genes while expression of 82 genes was significantly repressed. We found induction of genes known to be induced by PCN, such as enzymes involved in drug metabolism and transport. In addition, many genes were differentially expressed whose functions concerned intracellular metabolism, transport of essential small molecules, cell cycle, and redox balance. Our results support the idea that the domain of PXR-controlled gene networks may be even more extensive than currently thought and may extend to functions apart from xenobiotic metabolism.

Key Words: pregnenolone 16{alpha}-carbonitrile; pregnane X receptor; microarray; gene expression profiling.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Toxicol SciHome page
A. K. Goetz and D. J. Dix
Mode of Action for Reproductive and Hepatic Toxicity Inferred from a Genomic Study of Triazole Antifungals
Toxicol. Sci., August 1, 2009; 110(2): 449 - 462.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
J.-Y. Cho, D. W. Kang, X. Ma, S.-H. Ahn, K. W. Krausz, H. Luecke, J. R. Idle, and F. J. Gonzalez
Metabolomics reveals a novel vitamin E metabolite and attenuated vitamin E metabolism upon PXR activation
J. Lipid Res., May 1, 2009; 50(5): 924 - 937.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
D. Gupta, M. Venkatesh, H. Wang, S. Kim, M. Sinz, G. L. Goldberg, K. Whitney, C. Longley, and S. Mani
Expanding the Roles for Pregnane X Receptor in Cancer: Proliferation and Drug Resistance in Ovarian Cancer
Clin. Cancer Res., September 1, 2008; 14(17): 5332 - 5340.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
N. Kiyosawa, J. C. Kwekel, L. D. Burgoon, K. J. Williams, C. Tashiro, B. Chittim, and T. R. Zacharewski
o,p'-DDT Elicits PXR/CAR-, Not ER-, Mediated Responses in the Immature Ovariectomized Rat Liver
Toxicol. Sci., February 1, 2008; 101(2): 350 - 363.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
Y. Chen, Y. Tang, M.-T. Wang, S. Zeng, and D. Nie
Human Pregnane X Receptor and Resistance to Chemotherapy in Prostate Cancer
Cancer Res., November 1, 2007; 67(21): 10361 - 10367.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
X. Ma, Y. Shah, C. Cheung, G. L. Guo, L. Feigenbaum, K. W. Krausz, J. R. Idle, and F. J. Gonzalez
The Pregnane X Receptor Gene-Humanized Mouse: A Model for Investigating Drug-Drug Interactions Mediated by Cytochromes P450 3A
Drug Metab. Dispos., February 1, 2007; 35(2): 194 - 200.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.