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 Eltom, S. E.
Right arrow Articles by Jefcoate, C. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Eltom, S. E.
Right arrow Articles by Jefcoate, C. R.

Vol. 55, Issue 3, 594-604, March 1999

Regulation of Cytochrome P-450 (CYP) 1B1 in Mouse Hepa-1 Variant Cell Lines: A Possible Role for Aryl Hydrocarbon Receptor Nuclear Translocator (ARNT) as a Suppressor of CYP1B1 Gene Expression

Sakina E. Eltom, Leying Zhang, and Colin R. Jefcoate

Center for Environmental Toxicology and Department of Pharmacology, University of Wisconsin Medical School, Madison, Wisconsin

Cytochrome P-450 (CYP) 1B1 expression in mouse hepatoma (Hepa-1) wild-type (WT) cells was compared with responses in Hepa-1 variants LA1 and LA2, which, respectively, exhibit low aryl hydrocarbon receptor (AhR) level and defective AhR nuclear translocator (ARNT) protein. 10T1/2 mouse embryo fibroblasts express predominantly CYP1B1 and at a 100 times higher level than in Hepa-1 cells, whereas they express about 300-fold lower CYP1A1 than Hepa-1 cells. The expression of CYP1B1 in WT and LA1 variant, although at a much lower level, follows that of CYP1A1, reflecting their common regulation through the AhR. The LA2 (ARNT-defective) cells showed a major difference between CYP1B1 and CYP1A1 expression. Although CYP1A1 mRNA levels in LA2 were extremely low and unresponsive to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), basal CYP1B1 mRNA and protein were expressed at levels similar to those seen in TCDD-induced WT. The elevated basal CYP1B1 mRNA in LA2 cells decreased by 50% after transient transfection of ARNT cDNA, in parallel with substantial restoration of CYP1A1 induction. This implicates ARNT as a suppressor of CYP1B1 basal expression in Hepa cells. In transient CYP1B1-luciferase constructs in LA2 cells, ARNT shows stimulatory effects in the enhancer region but an inhibitory effect on the proximal promoter. Two CYP1B1 enhancer elements [xenobiotic-responsive element (XRE) 1/2 and XRE4] formed TCDD-unresponsive complexes of similar mobility to TCDD-stimulated AhR-ARNT complex with XRE5. However, because these two complexes were formed to the same extent in LA2 as in WT cells, they cannot be due to ARNT or contribute to ARNT-regulated suppression.

Copyright © 1999 by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
Y. R. Dale and S. E. Eltom
Calpain Mediates the Dioxin-Induced Activation and Down-Regulation of the Aryl Hydrocarbon Receptor
Mol. Pharmacol., November 1, 2006; 70(5): 1481 - 1487.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
D. R. Boverhof, E. Tam, A. S. Harney, R. B. Crawford, N. E. Kaminski, and T. R. Zacharewski
2,3,7,8-Tetrachlorodibenzo-p-dioxin Induces Suppressor of Cytokine Signaling 2 in Murine B Cells
Mol. Pharmacol., December 1, 2004; 66(6): 1662 - 1670.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
M. C. Larsen, P. B. Brake, R. S. Pollenz, and C. R. Jefcoate
Linked Expression of Ah Receptor, ARNT, CYP1A1, and CYP1B1 in Rat Mammary Epithelia, in Vitro, Is Each Substantially Elevated by Specific Extracellular Matrix Interactions that Precede Branching Morphogenesis
Toxicol. Sci., November 1, 2004; 82(1): 46 - 61.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
Y. V. Sun, D. R. Boverhof, L. D. Burgoon, M. R. Fielden, and T. R. Zacharewski
Comparative analysis of dioxin response elements in human, mouse and rat genomic sequences
Nucleic Acids Res., August 24, 2004; 32(15): 4512 - 4523.
[Abstract] [Full Text] [PDF]

Home page
 Toxicol SciHome page
S. A. Larsen-Su and D. E. Williams
Transplacental Exposure to Indole-3-carbinol Induces Sex-Specific Expression of CYP1A1 and CYP1B1 in the Liver of Fischer 344 Neonatal Rats
Toxicol. Sci., December 1, 2001; 64(2): 162 - 168.
[Abstract] [Full Text] [PDF]

Home page
 Drug Metab. Dispos.Home page
S. D. Spivack, G. J. Hurteau, A. A. Reilly, K. M. Aldous, X. Ding, and L. S. Kaminsky
CYP1B1 Expression in Human Lung
Drug Metab. Dispos., June 1, 2001; 29(6): 916 - 922.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
S. E. Shehin, R. O. Stephenson, and W. F. Greenlee
Transcriptional Regulation of the Human CYP1B1 Gene. EVIDENCE FOR INVOLVEMENT OF AN ARYL HYDROCARBON RECEPTOR RESPONSE ELEMENT IN CONSTITUTIVE EXPRESSION
J. Biol. Chem., March 15, 2000; 275(10): 6770 - 6776.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
B. A. Bejjani, D. W. Stockton, R. A. Lewis, K. F. Tomey, D. K. Dueker, M. Jabak, W. F. Astle, and J. R. Lupski
Multiple CYP1B1 mutations and incomplete penetrance in an inbred population segregating primary congenital glaucoma suggest frequent de novo events and a dominant modifier locus
Hum. Mol. Genet., February 12, 2000; 9(3): 367 - 374.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
J. K. Kerzee and K. S. Ramos
Constitutive and Inducible Expression of Cyp1a1 and Cyp1b1 in Vascular Smooth Muscle Cells: Role of the Ahr bHLH/PAS Transcription Factor
Circ. Res., September 28, 2001; 89(7): 573 - 582.
[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 © 1999 by the American Society for Pharmacology and Experimental Therapeutics