This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
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
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Morel, Y.
Right arrow Articles by Barouki, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Morel, Y.
Right arrow Articles by Barouki, R.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*BENZO(A)PYRENE
*HYDROGEN PEROXIDE

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 1999, p. 6825-6832, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

An Autoregulatory Loop Controlling CYP1A1 Gene Expression: Role of H2O2 and NFI

Yannick Morel,1 Nicolas Mermod,2 and Robert Barouki1,*

INSERM U490, Université Paris V-René Descartes, Centre Universitaire des Saints-Pères, 75006 Paris, France,1 and Laboratoire de Biotechnologie Moléculaire, Institut de Biologie Animale et Centre de Biotechnologie, UNIL-EPFL, Université de Lausanne, 1015 Lausanne, Switzerland2

Cytochrome P450 1A1 (CYP1A1), like many monooxygenases, can produce reactive oxygen species during its catalytic cycle. Apart from the well-characterized xenobiotic-elicited induction, the regulatory mechanisms involved in the control of the steady-state activity of CYP1A1 have not been elucidated. We show here that reactive oxygen species generated from the activity of CYP1A1 limit the levels of induced CYP1A1 mRNAs. The mechanism involves the repression of the CYP1A1 gene promoter activity in a negative-feedback autoregulatory loop. Indeed, increasing the CYP1A1 activity by transfecting CYP1A1 expression vectors into hepatoma cells elicited an oxidative stress and led to the repression of a reporter gene driven by the CYP1A1 gene promoter. This negative autoregulation is abolished by ellipticine (an inhibitor of CYP1A1) and by catalase (which catalyzes H2O2 catabolism), thus implying that H2O2 is an intermediate. Down-regulation is also abolished by the mutation of the proximal nuclear factor I (NFI) site in the promoter. The transactivating domain of NFI/CTF was found to act in synergy with the arylhydrocarbon receptor pathway during the induction of CYP1A1 by 2,3,7,8-tetrachloro-p-dibenzodioxin. Using an NFI/CTF-Gal4 fusion, we show that NFI/CTF transactivating function is decreased by a high activity of CYP1A1. This regulation is also abolished by catalase or ellipticine. Consistently, the transactivating function of NFI/CTF is repressed in cells treated with H2O2, a novel finding indicating that the transactivating domain of a transcription factor can be targeted by oxidative stress. In conclusion, an autoregulatory loop leads to the fine tuning of the CYP1A1 gene expression through the down-regulation of NFI activity by CYP1A1-based H2O2 production. This mechanism allows a limitation of the potentially toxic CYP1A1 activity within the cell.

* Corresponding author. Mailing address: INSERM U490, Université Paris V-René Descartes, Centre Universitaire des Saints-Pères, 45, rue des Saints-Pères, 75006 Paris, France. Phone: 33-1 42 86 20 75. Fax: 33-1 42 86 20 72. E-mail: robert.barouki{at}biomedicale.univ-paris5.fr.

Molecular and Cellular Biology, October 1999, p. 6825-6832, Vol. 19, No. 10
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Chiaro, C. R., Patel, R. D., Marcus, C. B., Perdew, G. H. (2007). Evidence for an Aryl Hydrocarbon Receptor-Mediated Cytochrome P450 Autoregulatory Pathway. Mol. Pharmacol. 72: 1369-1379 [Abstract] [Full Text]  
  • Gao, S., Zhao, Y., Kong, L., Toselli, P., Chou, I.-N., Stone, P., Li, W. (2007). Cloning and Characterization of the Rat Lysyl Oxidase Gene Promoter: IDENTIFICATION OF CORE PROMOTER ELEMENTS AND FUNCTIONAL NUCLEAR FACTOR I-BINDING SITES. J. Biol. Chem. 282: 25322-25337 [Abstract] [Full Text]  
  • Gorter, J. A., van Vliet, E. A., Aronica, E., Breit, T., Rauwerda, H., Lopes da Silva, F. H., Wadman, W. J. (2006). Potential New Antiepileptogenic Targets Indicated by Microarray Analysis in a Rat Model for Temporal Lobe Epilepsy. J. Neurosci. 26: 11083-11110 [Abstract] [Full Text]  
  • Kang, H. J., Kim, H. J., Kim, S. K., Barouki, R., Cho, C.-H., Khanna, K. K., Rosen, E. M., Bae, I. (2006). BRCA1 Modulates Xenobiotic Stress-inducible Gene Expression by Interacting with ARNT in Human Breast Cancer Cells. J. Biol. Chem. 281: 14654-14662 [Abstract] [Full Text]  
  • Sinha, A., Muthiah, K., Jiang, W., Couroucli, X., Barrios, R., Moorthy, B. (2005). Attenuation of Hyperoxic Lung Injury by the CYP1A Inducer {beta}-Naphthoflavone. Toxicol Sci 87: 204-212 [Abstract] [Full Text]  
  • Bessette, E. E., Fasco, M. J., Pentecost, B. T., Kaminsky, L. S. (2005). MECHANISMS OF ARSENITE-MEDIATED DECREASES IN BENZO[K]FLUORANTHENE-INDUCED HUMAN CYTOCHROME P4501A1 LEVELS IN HEPG2 CELLS. Drug Metab. Dispos. 33: 312-320 [Abstract] [Full Text]  
  • Georgiadis, P., Topinka, J., Vlachodimitropoulos, D., Stoikidou, M., Gioka, M., Stephanou, G., Autrup, H., Demopoulos, N. A., Katsouyanni, K., Sram, R., Kyrtopoulos, S. A. (2005). Interactions between CYP1A1 polymorphisms and exposure to environmental tobacco smoke in the modulation of lymphocyte bulky DNA adducts and chromosomal aberrations. Carcinogenesis 26: 93-101 [Abstract] [Full Text]  
  • Jiang, W., Welty, S. E., Couroucli, X. I., Barrios, R., Kondraganti, S. R., Muthiah, K., Yu, L., Avery, S. E., Moorthy, B. (2004). Disruption of the Ah Receptor Gene Alters the Susceptibility of Mice to Oxygen-Mediated Regulation of Pulmonary and Hepatic Cytochromes P4501A Expression and Exacerbates Hyperoxic Lung Injury. J. Pharmacol. Exp. Ther. 310: 512-519 [Abstract] [Full Text]  
  • Gouedard, C., Barouki, R., Morel, Y. (2004). Dietary Polyphenols Increase Paraoxonase 1 Gene Expression by an Aryl Hydrocarbon Receptor-Dependent Mechanism. Mol. Cell. Biol. 24: 5209-5222 [Abstract] [Full Text]  
  • Marchand, A., Barouki, R., Garlatti, M. (2004). Regulation of NAD(P)H:Quinone Oxidoreductase 1 Gene Expression by CYP1A1 Activity. Mol. Pharmacol. 65: 1029-1037 [Abstract] [Full Text]  
  • Merrill, C. L., Ni, H., Yoon, L. W., Tirmenstein, M. A., Narayanan, P., Benavides, G. R., Easton, M. J., Creech, D. R., Hu, C. X., McFarland, D. C., Hahn, L. M., Thomas, H. C., Morgan, K. T. (2002). Etomoxir-Induced Oxidative Stress in HepG2 Cells Detected by Differential Gene Expression Is Confirmed Biochemically. Toxicol Sci 68: 93-101 [Abstract] [Full Text]  
  • Couroucli, X. I., Welty, S. E., Geske, R. S., Moorthy, B. (2002). Regulation of Pulmonary and Hepatic Cytochrome P4501A Expression in the Rat by Hyperoxia: Implications for Hyperoxic Lung Injury. Mol. Pharmacol. 61: 507-515 [Abstract] [Full Text]  
  • Ke, S., Rabson, A. B., Germino, J. F., Gallo, M. A., Tian, Y. (2001). Mechanism of Suppression of Cytochrome P-450 1A1 Expression by Tumor Necrosis Factor-alpha and Lipopolysaccharide. J. Biol. Chem. 276: 39638-39644 [Abstract] [Full Text]  
  • Bonvallot, V., Baeza-Squiban, A., Baulig, A., Brulant, S., Boland, S., Muzeau, F., Barouki, R., Marano, F. (2001). Organic Compounds from Diesel Exhaust Particles Elicit a Proinflammatory Response in Human Airway Epithelial Cells and Induce Cytochrome p450 1A1 Expression. Am. J. Respir. Cell Mol. Bio. 25: 515-521 [Abstract] [Full Text]  
  • Hirsch-Ernst, K. I., Schlaefer, K., Bauer, D., Heder, A. F., Kahl, G. F. (2001). Repression of Phenobarbital-Dependent CYP2B1 mRNA Induction by Reactive Oxygen Species in Primary Rat Hepatocyte Cultures. Mol. Pharmacol. 59: 1402-1409 [Abstract] [Full Text]  
  • Coumoul, X., Diry, M., Robillot, C., Barouki, R. (2001). Differential Regulation of Cytochrome P450 1A1 and 1B1 by a Combination of Dioxin and Pesticides in the Breast Tumor Cell Line MCF-7. Cancer Res. 61: 3942-3948 [Abstract] [Full Text]  
  • Morel, Y., Coumoul, X., Nalpas, A., Barouki, R. (2001). Nuclear Factor I/CCAAT Box Transcription Factor trans-Activating Domain Is a Negative Sensor of Cellular Stress. Mol. Pharmacol. 58: 1239-1246 [Abstract] [Full Text]  
  • Morel, Y., de Waziers, I., Barouki, R. (2000). A Repressive Cross-Regulation between Catalytic and Promoter Activities of the CYP1A1 and CYP2E1 Genes: Role of H2O2. Mol. Pharmacol. 57: 1158-1164 [Abstract] [Full Text]  
  • Zhang, J., Zhang, Q.-Y., Guo, J., Zhou, Y., Ding, X. (2000). Identification and Functional Characterization of a Conserved, Nuclear Factor 1-like Element in the Proximal Promoter Region of CYP1A2 Gene Specifically Expressed in the Liver and Olfactory Mucosa. J. Biol. Chem. 275: 8895-8902 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»