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Regulation of GSK‐3β by calpain in the 3‐nitropropionic acid model
Author(s) -
CrespoBiel N.,
Camins A.,
GutiérrezCuesta J.,
Melchiorri D.,
Nicoletti F.,
Pallàs M.,
Canudas A.M.
Publication year - 2010
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.20691
Subject(s) - calpain , gsk 3 , chemistry , microbiology and biotechnology , cyclin dependent kinase 5 , programmed cell death , phosphorylation , glycogen synthase , cleavage (geology) , neuroscience , biochemistry , protein kinase a , biology , apoptosis , enzyme , mitogen activated protein kinase kinase , fracture (geology) , paleontology
Glycogen synthase kinase‐3β (GSK‐3β) is a crucial component in the cascade of events that culminate in a range of neurodegenerative 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‐3β regulation has not been demonstrated. Here we studied changes in total GSK‐3β protein levels and GSK‐3β phosphorylation at Ser‐9 in this model. The 3‐NP treatment induced GSK‐3β 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‐3β 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‐3β in the 3‐NP toxicity pathway. On the basis of our findings, we propose that calpain may modulate 3‐NP‐induced neuronal loss. © 2009 Wiley‐Liss, Inc.