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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleCellular and Molecular

Chromatin Remodeling by Rosuvastatin Normalizes TSC2-/meth Cell Phenotype through the Expression of Tuberin

Elena Lesma, Silvia Ancona, Emanuela Orpianesi, Vera Grande, Anna Maria Di Giulio and Alfredo Gorio
Journal of Pharmacology and Experimental Therapeutics May 2013, 345 (2) 180-188; DOI: https://doi.org/10.1124/jpet.113.203141
Elena Lesma
Laboratories of Pharmacology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Silvia Ancona
Laboratories of Pharmacology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Emanuela Orpianesi
Laboratories of Pharmacology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vera Grande
Laboratories of Pharmacology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Anna Maria Di Giulio
Laboratories of Pharmacology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alfredo Gorio
Laboratories of Pharmacology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy
  • 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

Tuberous sclerosis complex (TSC) is a multi-systemic syndrome caused by mutations in TSC1 or TSC2 gene. In TSC2-null cells, Rheb, a member of the Ras family of GTPases, is constitutively activated. Statins inhibit 3-hydroxy-3-methylglutaryl coenzyme A reductase and block the synthesis of isoprenoid lipids with inhibition of Rheb farnesylation and RhoA geranylgeranylation. The effects of rosuvastatin on the function of human TSC2−/− and TSC2-/meth α-actin smooth muscle (ASM) cells have been investigated. The TSC2−/− and TSC2-/meth ASM cells, previously isolated in our laboratory from the renal angiomyolipoma of two TSC patients, do not express tuberin and bear loss of heterozigosity caused by a double hit on TSC2 and methylation of TSC2 promoter, respectively. Exposure to rosuvastatin affected TSC2-/meth ASM cell growth and promoted tuberin expression by acting as a demethylating agent. This occurred without changes in interleukin release. Rosuvastatin also reduced RhoA activation in TSC2-/meth ASM cells, and it required coadministration with the specific mTOR (mammalian target of rapamycin) inhibitor rapamycin to be effective in TSC2−/− ASM cells. Rapamycin enhanced rosuvastatin effect in inhibiting cell proliferation in TSC2−/− and TSC2-/meth ASM cells. Rosuvastatin alone did not alter phosphorylation of S6 and extracellular signal-regulated kinase (ERK), and at the higher concentration, rosuvastatin and rapamycin slightly decreased ERK phosphorylation. These results suggest that rosuvastatin may potentially represent a treatment adjunct to the therapy with mTOR inhibitors now in clinical development for TSC. In particular, rosuvastatin appears useful when the disease is originated by epigenetic defects.

Footnotes

    • Received January 9, 2013.
    • Accepted February 19, 2013.
  • This work was supported by Associazione Italiana Linfangioleiomiomatosi AILAM (to A.G. and E.L.); Associazione Sclerosi Tuberosa (to E.L.); and Accordo Quadro di Collaborazione tra Università Lombarde from Lombardy Region (Research Collaborative Program between Lombard Universities and Region; to A.G.).

  • dx.doi.org/10.1124/jpet.113.203141.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 345 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 345, Issue 2
1 May 2013
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • 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 Journal of Pharmacology and Experimental Therapeutics 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.
Chromatin Remodeling by Rosuvastatin Normalizes TSC2-/meth Cell Phenotype through the Expression of Tuberin
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleCellular and Molecular

Rosuvastatin Epigenetic Effect on TSC2-/meth Cells

Elena Lesma, Silvia Ancona, Emanuela Orpianesi, Vera Grande, Anna Maria Di Giulio and Alfredo Gorio
Journal of Pharmacology and Experimental Therapeutics May 1, 2013, 345 (2) 180-188; DOI: https://doi.org/10.1124/jpet.113.203141

Citation Manager Formats

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

Share
Research ArticleCellular and Molecular

Rosuvastatin Epigenetic Effect on TSC2-/meth Cells

Elena Lesma, Silvia Ancona, Emanuela Orpianesi, Vera Grande, Anna Maria Di Giulio and Alfredo Gorio
Journal of Pharmacology and Experimental Therapeutics May 1, 2013, 345 (2) 180-188; DOI: https://doi.org/10.1124/jpet.113.203141
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • Anisodamine Ameliorates Acute Lung Injury
  • ACE2 Inhibits LPS-Caused Lung Fibrosis
  • ML355 Effects on Platelets
Show more Cellular and Molecular

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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

Copyright © 2022 by the American Society for Pharmacology and Experimental Therapeutics