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

Sporogen, S14-95, and S-Curvularin, Three Inhibitors of Human Inducible Nitric-Oxide Synthase Expression Isolated from Fungi

Ying Yao, Michael Hausding, Gerhard Erkel, Timm Anke, Ulrich Förstermann and Hartmut Kleinert
Molecular Pharmacology February 2003, 63 (2) 383-391; DOI: https://doi.org/10.1124/mol.63.2.383
Ying Yao
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Hausding
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Gerhard Erkel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Timm Anke
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ulrich Förstermann
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hartmut Kleinert
  • 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

The induction of human inducible nitric-oxide synthase (iNOS) expression depends (among other factors) on activation of the signal transducer and activator of transcription 1 (STAT1) pathway. Therefore, the STAT1 pathway may be an appropriate target for the development of inhibitors of iNOS expression. HeLa S3 cells transiently transfected with a γ-activated site (GAS)/interferon-stimulated response element-driven reporter gene construct were used as the primary screening system. Using this system, three novel inhibitors of interferon-γ-dependent gene expression, namely, sporogen, S14-95, andS-curvularin, were isolated from differentPenicillium species. These three compounds also inhibited cytokine-induced, GAS-dependent reporter gene expression in stably transfected human A549/8-pGASLuc cells, confirming the data obtained with the above-mentioned screening system. Furthermore, in A549/8 cells, sporogen, S14-95, and S-curvularin inhibited cytokine-induced activity of the human iNOS promoter [a 16-kilobase (kb) fragment in stably transfected A549/8-pNOS2(16)Luc cells], cytokine-induced iNOS mRNA expression, and cytokine-induced nitric oxide (NO) production in a concentration-dependent manner. The proliferation of A549/8 cells, and the activity of the human eNOS promoter (a 3.5-kb fragment in stably transfected ECV-pNOS III-Hu-3500-Luc cells), were only influenced marginally by the three compounds. Sporogen, S14-95, and S-curvularin also inhibited cytokine-induced activation of STAT1α in A549/8 cells. In conclusion, sporogen, S14-95, and S-curvularin represent new transcriptionally based inhibitors of iNOS-dependent NO production, acting on the Janus tyrosine kinase-STAT pathway. These compounds may represent lead structures for the development of drugs inhibiting iNOS-dependent overproduction of NO in pathophysiological situations.

Footnotes

  • This work was supported by Grant 8312-38 62 61/322a,b from the Innovation Foundation of the State of Rhineland-Palatinate, Grant Kl 1020/4-1 from the Deutsche Forschungsgemeinschaft (to H.K.), and by the Collaborative Research Center SFB 553 (Project A7 to H.K.). This article contains data from the thesis work of Y.Y.

  • Abbreviations:
    NO
    nitric oxide
    NOS
    nitric-oxide synthase
    eNOS
    endothelial nitric-oxide synthase
    iNOS
    inducible nitric-oxide synthase
    NF-κB
    nuclear factor-κB
    JAK
    janus kinase
    STAT
    signal transducer and activator of transcription
    IFN
    interferon
    kb
    kilobase(s)
    GAS
    γ-activated site
    BSA
    bovine serum albumin
    IL
    interleukin
    TNF
    tumor necrosis factor
    FCS
    fetal calf serum
    DMEM
    Dulbecco's modified Eagle's medium
    ISRE
    interferon-γ–stimulated responsive element
    CM
    cytokine mixture
    nt
    nucleotide
    SEAP
    secreted alkaline phosphatase
    OD
    optical density
    MTS
    3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide
    TBS
    Tris-buffered saline
    • Received August 12, 2002.
    • Accepted November 4, 2002.
  • 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: 63 (2)
Molecular Pharmacology
Vol. 63, Issue 2
1 Feb 2003
  • 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.
Sporogen, S14-95, and S-Curvularin, Three Inhibitors of Human Inducible Nitric-Oxide Synthase Expression Isolated from Fungi
(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

Sporogen, S14-95, and S-Curvularin, Three Inhibitors of Human Inducible Nitric-Oxide Synthase Expression Isolated from Fungi

Ying Yao, Michael Hausding, Gerhard Erkel, Timm Anke, Ulrich Förstermann and Hartmut Kleinert
Molecular Pharmacology February 1, 2003, 63 (2) 383-391; DOI: https://doi.org/10.1124/mol.63.2.383

Citation Manager Formats

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

Share
Research ArticleArticle

Sporogen, S14-95, and S-Curvularin, Three Inhibitors of Human Inducible Nitric-Oxide Synthase Expression Isolated from Fungi

Ying Yao, Michael Hausding, Gerhard Erkel, Timm Anke, Ulrich Förstermann and Hartmut Kleinert
Molecular Pharmacology February 1, 2003, 63 (2) 383-391; DOI: https://doi.org/10.1124/mol.63.2.383
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
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Mechanism of the selective action of paraherquamide A
  • Fatty Acid Amide Hydrolase in Cisplatin Nephrotoxicity
  • Use-Dependent Relief of A-887826 Inhibition
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