Regulation of GSK-3 beta by Calpain in the 3-Nitropropionic Acid Model

Crespo-Biel, N.; Camins, A.; Gutierrez-Cuesta, J.; Melchiorri, D.; Nicoletti, F.; Pallas, M.; Canudas, A. M.


Glycogen synthase kinase-3 beta (GSK-3 beta) is a crucial component in the cascade of events that culminate in a range of neuro-degenerative diseases. It is controlled by several pathways, including calpain-mediated cleavage. Calpain mediates in cell death induced by 3-nitropropionic acid (3-NP), but GSK-3 beta regulation has not been demonstrated. Here we studied changes in total GSK-3 beta protein levels and GSK-3 beta phosphorylation at Ser-9 in this model. The 3-NP treatment induced GSK-3 beta truncation. This regulation was dependent on calpain activation, since addition of calpeptin to the medium prevented this cleavage. While calpain inhibition prevented 3-NP-induced neuronal loss, inhibition of GSK-3 beta by SB-415286 did not. Furthermore, inhibition of cdk5, a known target of calpain involved in 3-NP-induced cell death, also failed to rescue neurons in our model. Our results point to a new target of calpain and indicate possible cross-talk between calpain and GSK-3 beta in the 3-NP toxicity pathway. On the basis of our findings, we propose that calpain may modulate 3-NP-induced neuronal loss. (C) 2009 Wiley-Liss, Inc.

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Título según WOS: ID WOS:000280739300010 Not found in local WOS DB
Título de la Revista: HIPPOCAMPUS
Volumen: 20
Número: 8
Editorial: Wiley
Fecha de publicación: 2010
Página de inicio: 962
Página final: 970


Notas: ISI