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

Differences in the Formation of PPARα-RXR/acoPPRE Complexes between Responsive and Nonresponsive Species upon Fibrate Administration

Cristina Rodríguez, Véronique Noé, Agatha Cabrero, Carlos J. Ciudad and Juan C. Laguna
Molecular Pharmacology July 2000, 58 (1) 185-193; DOI: https://doi.org/10.1124/mol.58.1.185
Cristina Rodríguez
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Véronique Noé
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Agatha Cabrero
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Carlos J. Ciudad
1 2
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juan C. Laguna
1 2
  • 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

Peroxisome proliferator-activated receptor-α (PPARα) is responsible for the hypolipidemic, peroxisome proliferation and carcinogenic effects of fibrates. Rats and mice are responsive, but guinea pigs and primates are resistant to the proliferative and carcinogenic effects of these drugs, but the hypolipidemic effect is still manifest. It is not yet clear whether humans should be considered unresponsive, and there is concern about the long-term safety of fibrates. We present molecular evidence for the reported resistance of human cells to peroxisome proliferation by describing a deficient interaction of nuclear extracts from human cells with an acyl-CoA oxidase (ACO)-peroxisome proliferator response element probe upon fibrate addition. Electrophoretic mobility shift assay analysis showed that ciprofibrate elicited a concentration-dependent increase in the binding of nuclear extracts from cells of rat (Morris) and human (HepG2) origin to an ACO-peroxisome proliferator response element probe, although in HepG2 cells the increase was of marginal statistical significance. In Morris cells, the increase was more marked than in HepG2 cells (4-fold versus 1.5-fold at 0.2 mM ciprofibrate), and maximal binding was achieved earlier in Morris (30 min) than in HepG2 cells (3 h). Morris cells responded to the addition of ciprofibrate by increasing the levels of ACO mRNA, whereas HepG2 did not. The ratio between PPARβ/PPARα mRNAs was higher in HepG2 cells than in Morris cells (3.2 versus 1.9), pointing to an antagonizing effect of PPARβ on PPARα activity. These results were obtained in untransfected cells expressing their own basal set of receptors. We also provide evidence of the translocation of PPARα from the cytosol to the nucleus upon activation by ciprofibrate.

Footnotes

    • Received August 23, 1999.
    • Accepted March 24, 2000.
  • Dr. Juan C. Laguna, Unidad de Farmacologı́a y Farmacognosia, Facultad de Farmacia, Universidad de Barcelona, Núcleo Universitario de Pedralbes, Barcelona E-08028, Spain. E-mail: laguna{at}farmacia.far.ub.es

  • This study was partly funded by grants from the FundacióPrivada Catalana de Nutrició i Lípids, Comision Interministerial de Ciencia y Tecnologia (SAF97-0215 to J.C.L. and SAF96-74 to C.J.C.), and from the “Generalitat de Catalunya,” SGR96-84 and SGR98-33. C.R. was a recipient of a fellowship from the Generalitat de Catalunya, and A.C. was a recipient of a fellowship from the Ministerio de Educacion y Cultura.

  • 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: 58 (1)
Molecular Pharmacology
Vol. 58, Issue 1
1 Jul 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.
Differences in the Formation of PPARα-RXR/acoPPRE Complexes between Responsive and Nonresponsive Species upon Fibrate Administration
(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

Differences in the Formation of PPARα-RXR/acoPPRE Complexes between Responsive and Nonresponsive Species upon Fibrate Administration

Cristina Rodríguez, Véronique Noé, Agatha Cabrero, Carlos J. Ciudad and Juan C. Laguna
Molecular Pharmacology July 1, 2000, 58 (1) 185-193; DOI: https://doi.org/10.1124/mol.58.1.185

Citation Manager Formats

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

Differences in the Formation of PPARα-RXR/acoPPRE Complexes between Responsive and Nonresponsive Species upon Fibrate Administration

Cristina Rodríguez, Véronique Noé, Agatha Cabrero, Carlos J. Ciudad and Juan C. Laguna
Molecular Pharmacology July 1, 2000, 58 (1) 185-193; DOI: https://doi.org/10.1124/mol.58.1.185
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
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • GABAAR Molecular Identity in Oligodendrocytes
  • Editing TOP2α Intron-19 5′ SS Circumvents Drug Resistance
  • SerpinA3N and drug induced liver injury
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