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
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
    • 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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleCELLULAR AND MOLECULAR

Temporal Activation of p42/44 Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase by Acetaldehyde in Rat Hepatocytes and Its Loss after Chronic Ethanol Exposure

Youn J. Lee, Annayya R. Aroor and Shivendra D. Shukla
Journal of Pharmacology and Experimental Therapeutics June 2002, 301 (3) 908-914; DOI: https://doi.org/10.1124/jpet.301.3.908
Youn J. Lee
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annayya R. Aroor
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shivendra D. Shukla
  • 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

Several cell-damaging effects of ethanol are due to its major metabolite acetaldehyde but its mechanisms are not known. We have studied the effect of acetaldehyde on p42/44 mitogen-activated protein kinase (MAPK) and p46/p54 c-Jun N-terminal kinase (JNK 1/2) in rat hepatocytes. Acetaldehyde caused peak activation of p42/44 MAPK at 10 min followed by JNK activation at 1 h. These responses were acetaldehyde dose-dependent (0.2–5 mM). There was a consistently higher activation of p46 JNK than p54 JNK. Ethanol also activated both p42/44 MAPK and p46/p54 JNK. The activation of JNK by ethanol, however, was not significantly affected by treatment of hepatocytes with 4-methylpyrazole, an alcohol dehydrogenase inhibitor. Cells treated with 200 mM ethanol for 1 h accumulated 0.35 ± 0.02 mM acetaldehyde, but the magnitude of JNK activation was greater than that expected with 0.35 mM acetaldehyde. Thus, ethanol-activated JNK may be both acetaldehyde-dependent and -independent. The activation of JNK by ethanol or acetaldehyde was insensitive to the treatment of hepatocytes with genistein (tyrosine kinase inhibitor) and 2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide (GF109203X) (protein kinase C inhibitor). Remarkably, in contrast to the above-mentioned effects on normal hepatocytes, acetaldehyde was unable to increase JNK activity in hepatocytes isolated from rats chronically fed ethanol for 6 weeks and indicated a loss of this acetaldehyde response. Thus, temporal activation of the p42/44 MAPK and p46/p54 JNK, the greater activation of p46 JNK than p54 JNK, and loss of JNK activation after chronic ethanol exposure indicate that these kinases are differentially affected by ethanol metabolite acetaldehyde.

Footnotes

  • This work was supported by a Grant AA11962 from National Institute on Alcohol Abuse and Alcoholism and was presented at the 2001 American Society for Pharmacology and Experimental Therapeutics meeting (FASEB J15:A571).

  • Abbreviations:
    MAPK
    mitogen-activated protein kinase
    JNK
    c-Jun N-terminal kinase
    MBP
    myelin basic protein
    FBS
    fetal bovine serum
    4-MP
    4-methylpyrazole
    PKC
    protein kinase C
    ADH
    alcohol dehydrogenase
    GF109203X
    2-[1-(3-dimethylaminopropyl)-1H-indol-3-yl]-3-(1H-indol-3-yl)maleimide
    • Received December 11, 2001.
    • Accepted February 13, 2002.
  • 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: 301 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 301, Issue 3
1 Jun 2002
  • 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 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.
Temporal Activation of p42/44 Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase by Acetaldehyde in Rat Hepatocytes and Its Loss after Chronic Ethanol Exposure
(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

Temporal Activation of p42/44 Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase by Acetaldehyde in Rat Hepatocytes and Its Loss after Chronic Ethanol Exposure

Youn J. Lee, Annayya R. Aroor and Shivendra D. Shukla
Journal of Pharmacology and Experimental Therapeutics June 1, 2002, 301 (3) 908-914; DOI: https://doi.org/10.1124/jpet.301.3.908

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

Temporal Activation of p42/44 Mitogen-Activated Protein Kinase and c-Jun N-Terminal Kinase by Acetaldehyde in Rat Hepatocytes and Its Loss after Chronic Ethanol Exposure

Youn J. Lee, Annayya R. Aroor and Shivendra D. Shukla
Journal of Pharmacology and Experimental Therapeutics June 1, 2002, 301 (3) 908-914; DOI: https://doi.org/10.1124/jpet.301.3.908
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
    • Experimental Procedures
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Zebrafish Gstp1 drug response
  • Comparison of Piceatannol with Resveratrol
  • Aldosterone synthesis in the heart
Show more Cellular and Molecular

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 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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics