Role of caspases, calpain and cdk5 in ammonia-induced cell death in developing brain cells.

Détails

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_C6BAA9C0B654
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Role of caspases, calpain and cdk5 in ammonia-induced cell death in developing brain cells.
Périodique
Neurobiology of Disease
Auteur(s)
Cagnon L., Braissant O.
ISSN
1095-953X
Statut éditorial
Publié
Date de publication
2008
Peer-reviewed
Oui
Volume
32
Numéro
2
Pages
281-292
Langue
anglais
Résumé
Hyperammonemia in neonates and infants causes irreversible damages in the developing CNS due to brain cell loss. Elucidating the mechanisms triggering ammonia-induced cell death in CNS is necessary for the development of neuroprotective strategies. We used reaggregated developing brain cell cultures derived from fetal rat telencephalon exposed to ammonia as an experimental model. Ammonia induced neuronal and oligodendroglial death, triggered apoptosis and activated caspases and calpain. Probably due to calpain activation, ammonia caused the cleavage of the cyclin-dependent kinase 5 activator, p35, to p25, the cdk5/p25 complex being known to lead to neurodegeneration. Roscovitine, a cdk5 inhibitor, protected neurons from ammonia-induced cell death. However, roscovitine also impaired axonal growth, probably through inhibition of the remaining cdk5/p35 activity, which is involved in neurite outgrowth. Thus, cdk5 appears as a promising therapeutic target for treating hyperammonemic newborns and infants, especially if one develops specific cdk5/p25 inhibitors.
Mots-clé
Ammonia, Animals, Calpain, Caspases, Cell Death, Cells, Cultured, Cyclin-Dependent Kinase 5, Dose-Response Relationship, Drug, Embryo, Mammalian, Enzyme Inhibitors, Immunoprecipitation, L-Lactate Dehydrogenase, Molecular Weight, Nerve Tissue Proteins, Neurons, Prosencephalon, Rats, Rats, Sprague-Dawley, Time Factors
Pubmed
Web of science
Open Access
Oui
Création de la notice
15/07/2008 8:33
Dernière modification de la notice
20/08/2019 15:42
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