Skip to main content

Main menu

  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE

User menu

  • Log in
  • My Cart

Search

  • Advanced search
Journal of Neuroscience
  • Log in
  • My Cart
Journal of Neuroscience

Advanced Search

Submit a Manuscript
  • HOME
  • CONTENT
    • Early Release
    • Featured
    • Current Issue
    • Issue Archive
    • Collections
    • Podcast
  • ALERTS
  • FOR AUTHORS
    • Information for Authors
    • Fees
    • Journal Clubs
    • eLetters
    • Submit
  • EDITORIAL BOARD
  • ABOUT
    • Overview
    • Advertise
    • For the Media
    • Rights and Permissions
    • Privacy Policy
    • Feedback
  • SUBSCRIBE
PreviousNext
ARTICLE, Cellular/Molecular

Zinc-Induced Cortical Neuronal Death: Contribution of Energy Failure Attributable to Loss of NAD+ and Inhibition of Glycolysis

Christian T. Sheline, M. Margarita Behrens and Dennis W. Choi
Journal of Neuroscience 1 May 2000, 20 (9) 3139-3146; DOI: https://doi.org/10.1523/JNEUROSCI.20-09-03139.2000
Christian T. Sheline
1Department of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
M. Margarita Behrens
1Department of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Dennis W. Choi
1Department of Neurology and Center for the Study of Nervous System Injury, Washington University School of Medicine, St. Louis, Missouri 63110
  • 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

Excessive zinc influx may contribute to neuronal death after certain insults, including transient global ischemia. In light of evidence that levels of intracellular free Zn2+associated with neurotoxicity may be sufficient to inhibit glyceraldehyde-3-phosphate dehydrogenase (GAPDH), experiments were performed looking for reduced glycolysis and energy failure in cultured mouse cortical neurons subjected to lethal Zn2+exposure. As predicted, cultures exposed for 3–22 hr to 40 μm Zn2+ developed an early increase in levels of dihydroxy-acetone phosphate (DHAP) and fructose 1,6-bisphosphate (FBP) and a progressive loss of ATP levels, followed by neuronal cell death; furthermore, addition of the downstream glycolytic substrate pyruvate to the bathing medium attenuated the fall in ATP and neuronal death.

However, an alternative to direct Zn2+ inhibition of GAPDH was raised by the observation that Zn2+exposure also induced an early decrease in nicotinamide-adenine dinucleotide (NAD+) levels, an event itself capable of inhibiting GAPDH. Favoring this indirect mechanism of GAPDH inhibition, the neuroprotective effects of pyruvate addition were associated with normalization of cellular levels of NAD+, DHAP, and FBP. Zn2+-induced neuronal death was also attenuated by addition of the energy substrate oxaloacetate, the activator of pyruvate dehydrogenase, dichloroacetate, or the inhibitors of NAD+ catabolism, niacinamide or benzamide. Acetyl carnitine, α-keto butyrate, lactate, and β-hydroxy-butyrate did not attenuate Zn2+-induced neurotoxicity, perhaps because they could not regenerate NAD+ or be used for energy production in the presence of glucose.

  • pyruvate
  • niacinamide
  • energy depletion
  • PARS
  • ATP levels
  • GAPDH inhibition
View Full Text
Back to top

In this issue

The Journal of Neuroscience: 20 (9)
Journal of Neuroscience
Vol. 20, Issue 9
1 May 2000
  • Table of Contents
  • Index by author
Email

Thank you for sharing this Journal of Neuroscience 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.
Zinc-Induced Cortical Neuronal Death: Contribution of Energy Failure Attributable to Loss of NAD+ and Inhibition of Glycolysis
(Your Name) has forwarded a page to you from Journal of Neuroscience
(Your Name) thought you would be interested in this article in Journal of Neuroscience.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Print
View Full Page PDF
Citation Tools
Zinc-Induced Cortical Neuronal Death: Contribution of Energy Failure Attributable to Loss of NAD+ and Inhibition of Glycolysis
Christian T. Sheline, M. Margarita Behrens, Dennis W. Choi
Journal of Neuroscience 1 May 2000, 20 (9) 3139-3146; DOI: 10.1523/JNEUROSCI.20-09-03139.2000

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Respond to this article
Request Permissions
Share
Zinc-Induced Cortical Neuronal Death: Contribution of Energy Failure Attributable to Loss of NAD+ and Inhibition of Glycolysis
Christian T. Sheline, M. Margarita Behrens, Dennis W. Choi
Journal of Neuroscience 1 May 2000, 20 (9) 3139-3146; DOI: 10.1523/JNEUROSCI.20-09-03139.2000
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

Keywords

  • pyruvate
  • niacinamide
  • energy depletion
  • PARS
  • ATP levels
  • GAPDH inhibition

Responses to this article

Respond to this article

Jump to comment:

No eLetters have been published for this article.

Related Articles

Cited By...

More in this TOC Section

ARTICLE

  • Evidence for Long-Lasting Cholinergic Control of Gap Junctional Communication between Adrenal Chromaffin Cells
  • Menstrual Cycle-Dependent Neural Plasticity in the Adult Human Brain Is Hormone, Task, and Region Specific
  • Estrogen Modulates the Visceromotor Reflex and Responses of Spinal Dorsal Horn Neurons to Colorectal Stimulation in the Rat
Show more ARTICLE

Cellular/Molecular

  • Phosphorylation of RPT6 controls its ability to bind DNA and regulate gene expression in the hippocampus of male rats during memory formation
  • Inactivation of ERK1/2 signaling in dopaminergic neurons by map kinase phosphatase MKP3 regulates dopamine signaling and motivation for cocaine
  • NaX Channel Is a Physiological [Na+] Detector in Oxytocin- and Vasopressin-Releasing Magnocellular Neurosecretory Cells of the Rat Supraoptic Nucleus
Show more Cellular/Molecular
  • Home
  • Alerts
  • Visit Society for Neuroscience on Facebook
  • Follow Society for Neuroscience on Twitter
  • Follow Society for Neuroscience on LinkedIn
  • Visit Society for Neuroscience on Youtube
  • Follow our RSS feeds

Content

  • Early Release
  • Current Issue
  • Issue Archive
  • Collections

Information

  • For Authors
  • For Advertisers
  • For the Media
  • For Subscribers

About

  • About the Journal
  • Editorial Board
  • Privacy Policy
  • Contact
(JNeurosci logo)
(SfN logo)

Copyright © 2023 by the Society for Neuroscience.
JNeurosci Online ISSN: 1529-2401

The ideas and opinions expressed in JNeurosci do not necessarily reflect those of SfN or the JNeurosci Editorial Board. Publication of an advertisement or other product mention in JNeurosci should not be construed as an endorsement of the manufacturer’s claims. SfN does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of any material contained in JNeurosci.