Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • 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
  • Submit
  • 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
Drug Metabolism & Disposition
  • 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
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • 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
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

The Nrf2 Activator Oltipraz Also Activates the Constitutive Androstane Receptor

Matthew D. Merrell, Jonathan P. Jackson, Lisa M. Augustine, Craig D. Fisher, Angela L. Slitt, Jonathan M. Maher, Wendong Huang, David D. Moore, Youcai Zhang, Curtis D. Klaassen and Nathan J. Cherrington
Drug Metabolism and Disposition August 2008, 36 (8) 1716-1721; DOI: https://doi.org/10.1124/dmd.108.020867
Matthew D. Merrell
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jonathan P. Jackson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lisa M. Augustine
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Craig D. Fisher
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Angela L. Slitt
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jonathan M. Maher
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Wendong Huang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David D. Moore
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Youcai Zhang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Curtis D. Klaassen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathan J. Cherrington
  • 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

Oltipraz (OPZ) is a well known inducer of NAD(P)H:quinone oxidoreductase (NQO1) along with other enzymes that comprise the nuclear factor E2–related factor 2 (Nrf2) battery of detoxification genes. However, OPZ treatment also induces expression of CYP2B, a gene regulated by the constitutive androstane receptor (CAR). Therefore, this study was designed to determine whether OPZ induces gene expression in the mouse liver through activation of CAR in addition to Nrf2. OPZ increased the mRNA expression of both Cyp2b10 and Nqo1 in C57BL/6 mouse livers. As expected, in livers from Nrf2-/- mice, OPZ induction of Nqo1 was reduced, indicating Nqo1 induction is dependent on Nrf2 activation, whereas Cyp2b10 induction was unchanged. The robust induction of Cyp2b10 by OPZ in wild-type mice was completely absent in CAR-/- mice, revealing a CAR-dependent induction by OPZ. OPZ also induced transcription of the human CYP2B6 promoter-reporter containing the phenobarbital (PB) responsive element in mouse liver using an in vivo transcription assay. Additionally, OPZ induced in vivo nuclear accumulation of CAR at 3 h but, as with PB, was unable to reverse androstanol repression of mouse CAR constitutive activity in transiently transfected HepG2 cells. In summary, OPZ induces expression of Cyp2b10 and Nqo1 via the activation of CAR and Nrf2, respectively.

Footnotes

  • This work was supported by National Institutes of Health Grants ES011646 and ES006694 (to N.J.C.), ES09716 and ES09649 (to C.D.K.), and DK46546 (to D.D.M.).

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.108.020867.

  • ABBREVIATIONS: OPZ, oltipraz; GST, glutathione-S-transferase; NQO1, NAD(P)H:quinone oxidoreductase; Nrf2, nuclear factor E2-related factor 2; ARE/EpRE, antioxidant response element/electrophile response element; Keap1, Kelch-like ECH-associated protein 1; CAR, constitutive androstane receptor; TCPOBOP, 1,4-bis-[2-(3, 5-dichloropyridyloxy)] benzene; CITCO, 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl)oxime; PB, phenobarbital; RXR, retinoid X receptor; bDNA, branched DNA; mCAR, mouse constitutive androstane receptor; PBREM, phenobarbital responsive element; DMSO, dimethyl sulfoxide; ERK, extracellular signal-regulated kinase.

    • Received February 7, 2008.
    • Accepted May 7, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD 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

Drug Metabolism and Disposition: 36 (8)
Drug Metabolism and Disposition
Vol. 36, Issue 8
1 Aug 2008
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition 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.
The Nrf2 Activator Oltipraz Also Activates the Constitutive Androstane Receptor
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

The Nrf2 Activator Oltipraz Also Activates the Constitutive Androstane Receptor

Matthew D. Merrell, Jonathan P. Jackson, Lisa M. Augustine, Craig D. Fisher, Angela L. Slitt, Jonathan M. Maher, Wendong Huang, David D. Moore, Youcai Zhang, Curtis D. Klaassen and Nathan J. Cherrington
Drug Metabolism and Disposition August 1, 2008, 36 (8) 1716-1721; DOI: https://doi.org/10.1124/dmd.108.020867

Citation Manager Formats

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

Share
Research ArticleArticle

The Nrf2 Activator Oltipraz Also Activates the Constitutive Androstane Receptor

Matthew D. Merrell, Jonathan P. Jackson, Lisa M. Augustine, Craig D. Fisher, Angela L. Slitt, Jonathan M. Maher, Wendong Huang, David D. Moore, Youcai Zhang, Curtis D. Klaassen and Nathan J. Cherrington
Drug Metabolism and Disposition August 1, 2008, 36 (8) 1716-1721; DOI: https://doi.org/10.1124/dmd.108.020867
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • A PBPK model for CBD in adults and children
  • Antibiotics Induce Changes in the Expression of Rat DPGs
  • Metabolism of Efavirenz by P450s and UGTs in the Brain
Show more Articles

Similar Articles

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

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics