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

Morphine Induces Redox-Based Changes in Global DNA Methylation and Retrotransposon Transcription by Inhibition of Excitatory Amino Acid Transporter Type 3–Mediated Cysteine Uptake

Malav Trivedi, Jayni Shah, Nathaniel Hodgson, Hyang-Min Byun and Richard Deth
Molecular Pharmacology May 2014, 85 (5) 747-757; DOI: https://doi.org/10.1124/mol.114.091728
Malav Trivedi
Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts (M.T., J.S., N.H., R.D.); Center for Molecular Biology and Biotechnology, Florida Atlantic University, Jupiter, Florida (R.D.); and Department of Environmental Epidemiology, Harvard School of Public Health, Boston, Massachusetts (H.-M.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jayni Shah
Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts (M.T., J.S., N.H., R.D.); Center for Molecular Biology and Biotechnology, Florida Atlantic University, Jupiter, Florida (R.D.); and Department of Environmental Epidemiology, Harvard School of Public Health, Boston, Massachusetts (H.-M.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nathaniel Hodgson
Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts (M.T., J.S., N.H., R.D.); Center for Molecular Biology and Biotechnology, Florida Atlantic University, Jupiter, Florida (R.D.); and Department of Environmental Epidemiology, Harvard School of Public Health, Boston, Massachusetts (H.-M.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hyang-Min Byun
Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts (M.T., J.S., N.H., R.D.); Center for Molecular Biology and Biotechnology, Florida Atlantic University, Jupiter, Florida (R.D.); and Department of Environmental Epidemiology, Harvard School of Public Health, Boston, Massachusetts (H.-M.B.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard Deth
Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts (M.T., J.S., N.H., R.D.); Center for Molecular Biology and Biotechnology, Florida Atlantic University, Jupiter, Florida (R.D.); and Department of Environmental Epidemiology, Harvard School of Public Health, Boston, Massachusetts (H.-M.B.)
  • 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 + SI
  • PDF
Loading

Abstract

Canonically, opioids influence cells by binding to a G protein–coupled opioid receptor, initiating intracellular signaling cascades, such as protein kinase, phosphatidylinositol 3-kinase, and extracellular receptor kinase pathways. This results in several downstream effects, including decreased levels of the reduced form of glutathione (GSH) and elevated oxidative stress, as well as epigenetic changes, especially in retrotransposons and heterochromatin, although the mechanism and consequences of these actions are unclear. We characterized the acute and long-term influence of morphine on redox and methylation status (including DNA methylation levels) in cultured neuronal SH-SY5Y cells. Acting via μ-opioid receptors, morphine inhibits excitatory amino acid transporter type 3–mediated cysteine uptake via multiple signaling pathways, involving different G proteins and protein kinases in a temporal manner. Decreased cysteine uptake was associated with decreases in both the redox and methylation status of neuronal cells, as defined by the ratios of GSH to oxidized forms of glutathione and S-adenosylmethionine to S-adenosylhomocysteine levels, respectively. Further, morphine induced global DNA methylation changes, including CpG sites in long interspersed nuclear elements (LINE-1) retrotransposons, resulting in increased LINE-1 mRNA. Together, these findings illuminate the mechanism by which morphine, and potentially other opioids, can influence neuronal-cell redox and methylation status including DNA methylation. Since epigenetic changes are implicated in drug addiction and tolerance phenomenon, this study could potentially extrapolate to elucidate a novel mechanism of action for other drugs of abuse.

Footnotes

    • Received January 16, 2014.
    • Accepted February 25, 2014.
  • This work was supported by research grants to R.D. from A2 Corporation Limited and the National Institutes of Health National Institute on Drug Abuse [Grant R21-DA030225]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

  • This work has been previously presented at the following meeting: Trivedi M, Hodgson N, Shah J, and Deth R (2013) A novel redox-based epigenetic signaling mechanism for opioids; Experimental Biology Meeting 2013; 2013 Apr 20–23; Boston, MA.

  • dx.doi.org/10.1124/mol.114.091728.

  • ↵Embedded ImageThis article has supplemental material available at molpharm.aspetjournals.org.

  • Copyright © 2014 by 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: 85 (5)
Molecular Pharmacology
Vol. 85, Issue 5
1 May 2014
  • 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 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.
Morphine Induces Redox-Based Changes in Global DNA Methylation and Retrotransposon Transcription by Inhibition of Excitatory Amino Acid Transporter Type 3–Mediated Cysteine Uptake
(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

Morphine-Induced Epigenetic Changes via EAAT3

Malav Trivedi, Jayni Shah, Nathaniel Hodgson, Hyang-Min Byun and Richard Deth
Molecular Pharmacology May 1, 2014, 85 (5) 747-757; DOI: https://doi.org/10.1124/mol.114.091728

Citation Manager Formats

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

Share
Research ArticleArticle

Morphine-Induced Epigenetic Changes via EAAT3

Malav Trivedi, Jayni Shah, Nathaniel Hodgson, Hyang-Min Byun and Richard Deth
Molecular Pharmacology May 1, 2014, 85 (5) 747-757; DOI: https://doi.org/10.1124/mol.114.091728
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
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
  • Benzbromarone relaxes airway smooth muscle via BK activation
  • Relapsed-leukemia model with NT5C2/PRPS1 hotspot mutations
Show more Articles

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