Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons

User menu

  • Subscribe
  • Log in

Search

  • Advanced search
The Journal of Immunology
  • Other Publications
    • American Association of Immunologists
    • ImmunoHorizons
  • Subscribe
  • Log in
The Journal of Immunology

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Next in The JI
    • Archive
    • Brief Reviews
    • Pillars of Immunology
    • Translating Immunology
    • Most Read
    • Top Downloads
    • Annual Meeting Abstracts
  • COVID-19/SARS/MERS Articles
  • Info
    • About the Journal
    • For Authors
    • Journal Policies
    • Influence Statement
    • For Advertisers
  • Editors
  • Submit
    • Submit a Manuscript
    • Instructions for Authors
    • Journal Policies
  • Subscribe
    • Journal Subscriptions
    • Email Alerts
    • RSS Feeds
    • ImmunoCasts
  • More
    • Most Read
    • Most Cited
    • ImmunoCasts
    • AAI Disclaimer
    • Feedback
    • Help
    • Accessibility Statement
  • Follow The Journal of Immunology on Twitter
  • Follow The Journal of Immunology on RSS

Glucocorticoid-Induced Apoptosis of Thymocytes: Requirement of Proteasome-Dependent Mitochondrial Activity

Noriko Tonomura, Kelly McLaughlin, Lisa Grimm, Richard A. Goldsby and Barbara A. Osborne
J Immunol March 1, 2003, 170 (5) 2469-2478; DOI: https://doi.org/10.4049/jimmunol.170.5.2469
Noriko Tonomura
*Department of Veterinary and Animal Sciences and
†Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kelly McLaughlin
‡Department of Biology, Tufts University, Medford, MA 02155;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lisa Grimm
¶Center for Cancer Research, Massachusetts General Hospital, Boston, MA 02114
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard A. Goldsby
*Department of Veterinary and Animal Sciences and
§Department of Biology, Amherst College, Amherst, MA 01002; and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Barbara A. Osborne
*Department of Veterinary and Animal Sciences and
†Program in Molecular and Cellular Biology, University of Massachusetts, Amherst, MA 01003;
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Thymocytes undergo negative and positive selection during development in the thymus. During this selection process, the majority of thymocytes are eliminated by apoptosis through signaling via TCR or die by neglect, possibly mediated through glucocorticoids. In this study, we report that thymocytes require molecular oxygen to undergo apoptosis induced by dexamethasone (DEX), a synthetic glucocorticoid, and treatment with N-acetyl-l-cysteine (NAC), a thiol antioxidant, inhibits thymocyte apoptosis in vivo as well as ex vivo. We detected elevated intracellular levels of hydrogen peroxide (H2O2) during DEX-induced apoptosis, which is reduced by NAC treatment, indicating that the elevated levels of intracellular H2O2 are proapoptotic. We also show that loss of mitochondrial membrane potential, cytochrome c release, as well as caspase-3 activation induced by DEX are attenuated by NAC treatment. We identified the production site for H2O2 as the ubiquinone cycle at complex III of mitochondria by using various inhibitors of the mitochondrial electron transport chain, and we show that the cell death events mediated by mitochondria are also significantly reduced when the inhibitors were used. Through inhibition of the proteasome, we also show that the production of H2O2 and the cell death events mediated by mitochondria are regulated by proteosomal activities in DEX-induced thymocyte apoptosis. We conclude that in DEX-treated thymocytes, the increased production of H2O2 originates from mitochondria and is proapoptotic for cell death mediated by mitochondria. We also conclude that all the apoptotic events mediated by mitochondria are regulated by proteasomes.

  • Received September 9, 2002.
  • Accepted December 20, 2002.
  • Copyright © 2003 by The American Association of Immunologists
View Full Text
PreviousNext
Back to top

In this issue

The Journal of Immunology: 170 (5)
The Journal of Immunology
Vol. 170, Issue 5
1 Mar 2003
  • Table of Contents
  • About the Cover
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word about The Journal of Immunology.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Glucocorticoid-Induced Apoptosis of Thymocytes: Requirement of Proteasome-Dependent Mitochondrial Activity
(Your Name) has forwarded a page to you from The Journal of Immunology
(Your Name) thought you would like to see this page from the The Journal of Immunology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Glucocorticoid-Induced Apoptosis of Thymocytes: Requirement of Proteasome-Dependent Mitochondrial Activity
Noriko Tonomura, Kelly McLaughlin, Lisa Grimm, Richard A. Goldsby, Barbara A. Osborne
The Journal of Immunology March 1, 2003, 170 (5) 2469-2478; DOI: 10.4049/jimmunol.170.5.2469

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Glucocorticoid-Induced Apoptosis of Thymocytes: Requirement of Proteasome-Dependent Mitochondrial Activity
Noriko Tonomura, Kelly McLaughlin, Lisa Grimm, Richard A. Goldsby, Barbara A. Osborne
The Journal of Immunology March 1, 2003, 170 (5) 2469-2478; DOI: 10.4049/jimmunol.170.5.2469
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Innate Immunity Together with Duration of Antigen Persistence Regulate Effector T Cell Induction
  • Regulatory Roles of IL-2 and IL-4 in H4/Inducible Costimulator Expression on Activated CD4+ T Cells During Th Cell Development
  • Induction of CD4+ T Cell Apoptosis as a Consequence of Impaired Cytoskeletal Rearrangement in UVB-Irradiated Dendritic Cells
Show more CELLULAR IMMUNOLOGY AND IMMUNE REGULATION

Similar Articles

Navigate

  • Home
  • Current Issue
  • Next in The JI
  • Archive
  • Brief Reviews
  • Pillars of Immunology
  • Translating Immunology

For Authors

  • Submit a Manuscript
  • Instructions for Authors
  • About the Journal
  • Journal Policies
  • Editors

General Information

  • Advertisers
  • Subscribers
  • Rights and Permissions
  • Accessibility Statement
  • FAR 889
  • Privacy Policy
  • Disclaimer

Journal Services

  • Email Alerts
  • RSS Feeds
  • ImmunoCasts
  • Twitter

Copyright © 2022 by The American Association of Immunologists, Inc.

Print ISSN 0022-1767        Online ISSN 1550-6606