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Inhibition of the cdk5/p25 fragment formation may explain the antiapoptotic effects of melatonin in an experimental model of Parkinson's disease
Author(s) -
Alvira Daniel,
Tajes Marta,
Verdaguer Ester,
AcuñaCastroviejo Dario,
Folch Jaume,
Camins Antoni,
Pallas Mercè
Publication year - 2006
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2005.00308.x
Subject(s) - calpain , cyclin dependent kinase 5 , melatonin , apoptosis , caspase , microbiology and biotechnology , viability assay , programmed cell death , cleavage (geology) , biology , caspase 3 , chemistry , neuroscience , biochemistry , enzyme , cell cycle , paleontology , fracture (geology) , cyclin dependent kinase 2
In this study, the effects of melatonin on MPP + ‐treated cerebellar granule neurons (CGNs) in culture were investigated. Results showed that MPP + treatment significantly decreased cell viability and increased the apoptotic cell population at 24 and 48 hr. Calpain and caspase‐3 activation was also determined, with results showing a strong increase in calpain (74%) and caspase 3 activity (70%), as measured by α ‐spectrin cleavage and fluorometric and colorimetric analysis, respectively. There are several studies suggesting that the activation of the cdk5/p35 pathway at its cleavage to cdk5/p25 may play a role in neuronal cell death in neurodegenerative diseases. Moreover, these studies indicate that this cleavage is mediated by calpains, and that MPP + prompted an increase in cdk5 expression, as well as the cleavage of p35–p25, in a time‐dependent manner. 1 m m Melatonin not only reduced the neurotoxic effects of MPP + on cell viability, but also prevented apoptosis mediated by this Parkinsonian toxin in CGNs. 1 m m Melatonin reduced cdk5 expression, as well as the cleavage of p35–p25. These data indicate that melatonin possesses some neuro‐protective properties against MPP + ‐induced apoptosis. Moreover, these data suggest that the calpain/cdk5 signaling cascade has a potential role in the MPP + ‐mediated apoptotic process in CGNs.