English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Role of extracellular signal-regulated protein kinase in neuronal cell death induced by glutathione depletion in neuron/glia mesencephalic cultures

de Bernardo, S., Canals, S., Casarejos, M., Solana, R., Menendez, J., & Mena, M. (2004). Role of extracellular signal-regulated protein kinase in neuronal cell death induced by glutathione depletion in neuron/glia mesencephalic cultures. Journal of Neurochemistry, 91(3), 667-682. doi:10.1111/j.1471-4159.2004.02744.x.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-D763-E Version Permalink: http://hdl.handle.net/21.11116/0000-0005-4901-8
Genre: Journal Article

Files

show Files

Locators

show

Creators

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

Content

show
hide
Free keywords: -
 Abstract: To date, glutathione (GSH) depletion is the earliest biochemical alteration shown in brains of Parkinson‘s disease patients, but the role of GSH in dopamine cell survival is debated. In this study we show that GSH depletion, produced with GSH synthesis inhibitor, l-buthionine-(S,R)-sulfoximine (BSO), induces selectively neuronal cell death in neuron/glia, but not in neuronal-enriched midbrain cultures and that cell death occurs with characteristics of necrosis and apoptosis. BSO produces a dose- and time-dependent generation of reactive oxygen species (ROS) in neurons. BSO activates extracellular signal-regulated kinases (ERK-1/2), 4 and 6 h after treatment. MEK-1/2 and lipoxygenase (LOX) inhibitors, as well as ascorbic acid, prevent ERK-1/2 activation and neuronal loss, but the inhibition of nitric oxide sintase (NOS), cyclo-oxygenase (COX), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) does not have protective effects. Co-localization studies show that p-ERK-1/2 expression after BSO treatment increased in astrocytes and microglial cells, but not in neurons. Selective metabolic impairment of glial cells with fluoroacetate decreased ERK activation. However, blockade of microglial activation with minocycline did not. Our results indicate that neuronal death induced by GSH depletion is due to ROS-dependent activation of the ERK-1/2 signalling pathway in glial cells. These data may be of relevance in Parkinson‘s disease, where GSH depletion and glial dysfunction have been documented.

Details

show
hide
Language(s):
 Dates: 2004-11
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1111/j.1471-4159.2004.02744.x
BibTex Citekey: 3295
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Neurochemistry
  Other : J. Neurochem.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: New York : Raven Press [etc.]
Pages: - Volume / Issue: 91 (3) Sequence Number: - Start / End Page: 667 - 682 Identifier: ISSN: 0022-3042
CoNE: https://pure.mpg.de/cone/journals/resource/954925416956_1