Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Pharmacology
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Molecular Pharmacology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Visit molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

A Repressive Cross-Regulation between Catalytic and Promoter Activities of the CYP1A1 and CYP2E1Genes: Role of H2O2

Yannick Morel, Isabelle de Waziers and Robert Barouki
Molecular Pharmacology June 2000, 57 (6) 1158-1164;
Yannick Morel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Isabelle de Waziers
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert Barouki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Cytochrome P450 enzymes catalyze the first step of the metabolism and subsequent elimination of hydrophobic xenobiotics. However, the activity of some isoforms, among them CYP1A1 and CYP2E1, may result in cellular insults such as oxidative stress and activation of procarcinogen compounds into reactive metabolites. The regulation of the expression of these enzymes is therefore important. We have previously shown that the CYP1A1 gene promoter was repressed by oxidative stress. We show here that theCYP2E1 gene promoter is down-regulated by exogenous H2O2 addition and glutathione depletion. It is also repressed by the transfection of a CYP2E1 expression vector, which elicits an intracellular H2O2 generation. This autoregulation is limited by catalase (which catalyzes the catabolism of H2O2), thus implying H2O2 as a mediator of the negative feedback mechanism. Furthermore, we observed that the activity of CYP1A1 resulting either from the stimulation of the endogenous gene by benzo[a]pyrene treatment or from the transfection of an expression vector, repressed the activity of theCYP2E1 gene promoter. Conversely, CYP2E1 overexpression repressed the activity of the CYP1A1 gene promoter. In both cases, catalase and a specific inhibitor of one enzyme prevented the repression of the other. This suggests that the generation of H2O2 during the catalytic cycle of these enzymes is a mediator of the cross-regulatory mechanisms. These novel repressive mechanisms of autoregulation and cross-regulation using H2O2 as a common mediator may limit the potential toxicity resulting from high cytochrome P450 activity within the cell.

Footnotes

  • Send reprint requests to: Dr. Robert Barouki, Institut National de la Santé et de la Recherche Médicale U490, Université Paris V-René Descartes, Centre Universitaire des Saints-Pères, 45, rue des Saints-Pères, 75006 Paris, France. E-mail: robert.barouki{at}biomedicale.univ-paris5.fr

  • Abbreviations:
    BP
    benzo[a]pyrene
    ROS
    reactive oxygen species
    UTR
    untranslated region
    DCF
    2′,7′-dichlorofluorescein
    BSO
    l-buthionine-S,R-sulfoximine
    4-MP
    4-methlpyrrazole
    NFI
    nuclear factor I
    • Received October 5, 1999.
    • Accepted February 17, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

MolPharm articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Molecular Pharmacology: 57 (6)
Molecular Pharmacology
Vol. 57, Issue 6
1 Jun 2000
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Pharmacology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
A Repressive Cross-Regulation between Catalytic and Promoter Activities of the CYP1A1 and CYP2E1Genes: Role of H2O2
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

A Repressive Cross-Regulation between Catalytic and Promoter Activities of the CYP1A1 and CYP2E1Genes: Role of H2O2

Yannick Morel, Isabelle de Waziers and Robert Barouki
Molecular Pharmacology June 1, 2000, 57 (6) 1158-1164;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Research ArticleArticle

A Repressive Cross-Regulation between Catalytic and Promoter Activities of the CYP1A1 and CYP2E1Genes: Role of H2O2

Yannick Morel, Isabelle de Waziers and Robert Barouki
Molecular Pharmacology June 1, 2000, 57 (6) 1158-1164;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • CTS bias
  • Nelfinavir and PXR
  • P2X7 Positive Modulator Structure-Activity Relationship
Show more Article

Similar Articles

  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

Copyright © 2021 by the American Society for Pharmacology and Experimental Therapeutics