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Timing differences of signaling response in neuron cultures activated by glutamate analogue or free radicals.
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- Author(s): Boutahar N;Boutahar N; Reynaud E; Lassabliere F; Borg J
- Source:
Brain research [Brain Res] 2008 Jan 29; Vol. 1191, pp. 20-9. Date of Electronic Publication: 2007 Nov 17.
- Publication Type:
Comparative Study; Journal Article; Research Support, Non-U.S. Gov't
- Language:
English
- Additional Information
- Source:
Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 0045503 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-8993 (Print) Linking ISSN: 00068993 NLM ISO Abbreviation: Brain Res Subsets: MEDLINE
- Publication Information:
Original Publication: Amsterdam Elsevier/North-Holland Biomedical Press.
- Subject Terms:
- Abstract:
Oxidative stress and excitotoxicity are both involved in the pathogenesis of neuronal degenerative diseases like ALS. In order to compare their action, some key proteins involved in their respective signaling pathways, particularly ERK and p53, were analyzed in primary cultures of cortical neurons subjected to NMDA or H(2)O(2) treatment. Early ERK activation was detected after NMDA treatment and was maintained during 24 h, but not after H(2)O(2) treatment. Early p53 expression was also found after NMDA treatment but diminished later. On the other hand, it progressively increased from 6 h to 24 h after H(2)O(2) treatment. Blocking ERK1/2 activation with the upstream inhibitor U0126 inhibited NMDA-mediated p53 expression, suggesting that ERK1/2 signals drive the cells to apoptosis under these conditions. In order to identify the initial membrane target of these neurotoxins, PAK1 was analyzed. Early increase of PAK1 expression was measured after NMDA treatment and was still present after 24 h. Conversely increased PAK1 expression was only detected 24 h after H(2)O(2) treatment. In order to define the components through which NMDA or H(2)O(2) induce the final elements of these pathways, p21 and c-jun, we have performed a detailed functional analysis of c-jun and p21 promoters following plasmid transfection. Both p21 and c-jun were activated after NMDA treatment, but this activation was abolished after H(2)O(2) treatment. We conclude that NMDA induces an early effect that involves activation of p53, ERK, PAK1, p21 and c-jun. On the other hand, H(2)O(2) induces long-term p53 expression, late expression of PAK1 without activation of p21 promoter. The timing differences of the action of these neurotoxins may explain why the presence of both compounds is needed to induce neuronal death.
- Accession Number:
0 (Excitatory Amino Acid Agonists)
0 (Free Radicals)
0 (Neurotoxins)
0 (Oxidants)
0 (Proto-Oncogene Proteins c-jun)
0 (Tumor Suppressor Protein p53)
6384-92-5 (N-Methylaspartate)
BBX060AN9V (Hydrogen Peroxide)
EC 2.7.11.1 (p21-Activated Kinases)
EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
- Publication Date:
Date Created: 20071225 Date Completed: 20080519 Latest Revision: 20131121
- Publication Date:
20221213
- Accession Number:
10.1016/j.brainres.2007.11.016
- Accession Number:
18154926
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