English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Selective and persistent activation of extracellular signal-regulated protein kinase by nitric oxide in glial cells induces neuronal degeneration in glutathione-depleted midbrain cultures

Canals, S., Casarejos, M., de Bernardo, S., Solano, R., & Mena, M. (2003). Selective and persistent activation of extracellular signal-regulated protein kinase by nitric oxide in glial cells induces neuronal degeneration in glutathione-depleted midbrain cultures. Molecular and Cellular Neuroscience, 24(4), 1012-1026. doi:10.1016/j.mcn.2003.08.004.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-DAA1-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-692D-4
Genre: Journal Article

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Canals, S1, Author              
Casarejos , MJ, Author
de Bernardo, S, Author
Solano, RM, Author
Mena, MA, Author
Affiliations:
1External Organizations, ou_persistent22              

Content

show
hide
Free keywords: -
 Abstract: Intracellular glutathione (GSH) levels determine whether nitric oxide (NO) is neurotrophic for dopamine neurons or triggers a cell death cascade in primary midbrain cultures. We have investigated herein the role of the extracellular-signal regulated protein kinase (ERK) 1/2 pathway in this GSH switching effect. The short-lived NO donor DEA/NO induces a transient activation of ERK-1/2 that totally disappears 2 h after NO administration. The depletion of GSH increases and the supplementation of GSH suppresses ERK-1/2 activation in response to NO treatment. More interestingly, GSH depletion changes the kinetic of phosphorylation leading to a second prolonged phase of ERK-1/2 activation from 2 to 16 h after NO addition. This change of kinetic is ultimately responsible for NO toxicity under GSH-depleted conditions, because selective blockade of the second and persistent phase of activation prevents cell death. In addition, the only transient ERK activation, induced by NO under normal GSH conditions, did not cause ERK-dependent cell death. Immunocytochemical colocalization studies demonstrate that ERK activation takes place exclusively in glial cells, mainly in astrocytes and less frequently in oligodendrocytes and glial progenitors. Furthermore, glial cell elimination or inactivation in the culture, by gliotoxic drugs, abrogates NO-induced ERK activation. Our results indicate that neurotrophism of NO switches into neurotoxicity after GSH depletion due to persistent activation of the ERK-1/2 signaling pathway in glial cells. The implication of these results in pathological conditions like Parkinson‘s disease, where GSH depletion and NO overproduction have been documented, are discussed.

Details

show
hide
Language(s):
 Dates: 2003-12
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1016/j.mcn.2003.08.004
BibTex Citekey: 3296
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Molecular and Cellular Neuroscience
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Orlando, Fla. : Academic Press
Pages: - Volume / Issue: 24 (4) Sequence Number: - Start / End Page: 1012 - 1026 Identifier: ISSN: 1044-7431
CoNE: https://pure.mpg.de/cone/journals/resource/954922650153