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Regulation of GSK-3β by calpain in the 3-nitropropionic acid model.
- Source :
-
Hippocampus . Aug2010, Vol. 20 Issue 8, p962-970. 9p. - Publication Year :
- 2010
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 10509631
- Volume :
- 20
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Hippocampus
- Publication Type :
- Academic Journal
- Accession number :
- 64911626
- Full Text :
- https://doi.org/10.1002/hipo.20691