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
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
    • 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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Nitric Oxide Inhibits Matrix Metalloproteinase-2 Expression via the Induction of Activating Transcription Factor 3 in Endothelial Cells

Hsuan-Hsu Chen and Danny Ling Wang
Molecular Pharmacology May 2004, 65 (5) 1130-1140; DOI: https://doi.org/10.1124/mol.65.5.1130
Hsuan-Hsu Chen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Danny Ling Wang
  • 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

Nitric oxide (NO) has been shown to inhibit migration of cells in which various matrix metalloproteinases (MMPs) are involved. The underlying molecular mechanisms of this inhibition remain elusive. Endothelial cells (ECs) constitutively produce MMP-2. The effect of NO on MMP-2 expression was examined. A dose-dependent inhibition of MMP-2 mRNA level was demonstrated in ECs treated with NO. ECs infected with adenovirus carrying endothelial NO synthase (Ade-NOS) reduced MMP-2 expression. The inhibitory effect of NO on MMP-2 expression was a transcriptional event because NO reduced MMP-2 promoter activity. NO treatment of ECs consequently suppressed MMP-2 secretion revealed by zymographic assay. Functional analysis of MMP-2 promoter (1716 base pairs) indicated that the p53-binding site (-1659 to -1629) was crucial for MMP-2 promoter activity. Activating transcription factor 3 (ATF3) has been reported to act as a transcriptional repressor for p53. ECs treated with NO induced ATF3 expression. Consistently, Ade-NOS-infected ECs showed an increase of ATF3 level. Moreover, ECs either over-expressed ATF3 or, when treated with an ATF3 activator (MG-132; carbobenzoxy-l-leucyl-l-leucyl-l-leucinal), resulted in a repression of MMP-2 promoter activity. Because of MMP-2 suppression by NO, ECs treated with NO inhibited endothelial migration, a phenomenon similar to that of ECs treated with MMP-2 antibody or MG-132. These results indicate that NO-attenuating endothelial migration is mediated at least in part by its reduction of MMP-2 expression via the up-regulation of ATF3. This study provides a molecular basis that supports the notion that NO acts as a negative regulator in endothelial migration.

  • Received August 11, 2003.
  • Accepted February 10, 2004.
  • 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: 65 (5)
Molecular Pharmacology
Vol. 65, Issue 5
1 May 2004
  • 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.
Nitric Oxide Inhibits Matrix Metalloproteinase-2 Expression via the Induction of Activating Transcription Factor 3 in Endothelial Cells
(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

Nitric Oxide Inhibits Matrix Metalloproteinase-2 Expression via the Induction of Activating Transcription Factor 3 in Endothelial Cells

Hsuan-Hsu Chen and Danny Ling Wang
Molecular Pharmacology May 1, 2004, 65 (5) 1130-1140; DOI: https://doi.org/10.1124/mol.65.5.1130

Citation Manager Formats

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

Share
Research ArticleArticle

Nitric Oxide Inhibits Matrix Metalloproteinase-2 Expression via the Induction of Activating Transcription Factor 3 in Endothelial Cells

Hsuan-Hsu Chen and Danny Ling Wang
Molecular Pharmacology May 1, 2004, 65 (5) 1130-1140; DOI: https://doi.org/10.1124/mol.65.5.1130
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

  • Analgesic Effects and Mechanisms of Licochalcones
  • Induced Fit Ligand Binding to CYP3A4
  • Englerin A Inhibits T-Type Channels
Show more Article

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 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 © 2023 by the American Society for Pharmacology and Experimental Therapeutics