3-Nitropropionic acid activates calpain/cdk5 pathway in rat striatum

Crespo-Biel, Natalia; Camins, Antoni; Pelegri, Carme; Vilaplana, Jordi; Pallas, Merce; Canudas, Anna M.


3-Nitropropionic acid (3-NP) is a neurotoxin that inhibits mitochondrial complex II and is used in an experimental model of Huntington's disease. Treatment of rats with 3-NP 30 mg kg(-1) i.p. once a day for 5 days induced an increase in calpain activation in rat striatum, measured by the formation of 145 kDa fragment of alpha-spectrin breakdown and by an increase in enzymatic calpain activity. In this neurotoxic model, Western blot studies revealed that calpain activity increase was followed by changes in cyclin-dependent kinase 5 (cdk5) and its activator p25. Our results indicated, after 10 days of treatment with 3-NP, a decrease in myocyte enhancer factor phosphorylation, a neuronal prosurvival factor. Thus, a decrease in its expression indicates a new potential mechanism of neuronal cell death mediated by the neurotoxin 3-NP. Accordingly, in our study we demonstrated in rat striatum the activation of the calpain/cdk5/p25 pathway in the 3-NP model. Previous studies have linked the deregulation of cdk5 with neurodegenerative diseases, such as Alzheimer's and Parkinson's. We suggest that calpain/cdk5 activation could also be a common pathway activated in other neurodegenerative diseases, which is liable to be targeted. (c) 2007 Elsevier Ireland Ltd. All rights reserved.

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Título según WOS: ID WOS:000248152500016 Not found in local WOS DB
Título de la Revista: NEUROSCIENCE LETTERS
Volumen: 421
Número: 1
Fecha de publicación: 2007
Página de inicio: 77
Página final: 81


Notas: ISI