| Inhibition of the cdk5/p25 fragment formation may explain the antiapoptotic effects of melatonin in an experimental model of Parkinson's disease. | |
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MedLine Citation:
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PMID: 16499562 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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 alpha-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 mm Melatonin not only reduced the neurotoxic effects of MPP+ on cell viability, but also prevented apoptosis mediated by this Parkinsonian toxin in CGNs. 1 mm 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. |
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Authors:
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Daniel Alvira; Marta Tajes; Ester Verdaguer; Dario Acuña-Castroviejo; Jaume Folch; Antoni Camins; Mercè Pallas |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of pineal research Volume: 40 ISSN: 0742-3098 ISO Abbreviation: J. Pineal Res. Publication Date: 2006 Apr |
Date Detail:
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Created Date: 2006-02-27 Completed Date: 2006-05-30 Revised Date: 2009-11-19 |
Medline Journal Info:
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Nlm Unique ID: 8504412 Medline TA: J Pineal Res Country: Denmark |
Other Details:
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Languages: eng Pagination: 251-8 Citation Subset: IM |
Affiliation:
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Unitat de Farmacologia i Farmacognòsia, Facultat de Farmacia, Universitat de Barcelona, Nucli Universitari de Pedralbes, Barcelona, Spain. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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1-Methyl-4-phenylpyridinium
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pharmacology Animals Apoptosis / drug effects* Calpain / metabolism Caspase 3 Caspases / metabolism Cell Survival / drug effects Cells, Cultured Cerebellum / cytology Cyclin-Dependent Kinase 5 / metabolism Enzyme Activation Melatonin / pharmacology* Nerve Tissue Proteins / antagonists & inhibitors* Neurons / drug effects Parkinson Disease, Secondary / chemically induced Rats Rats, Sprague-Dawley |
| Chemical | |
Reg. No./Substance:
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0/Nerve Tissue Proteins; 0/neuronal Cdk5 activator (p25-p35); 48134-75-4/1-Methyl-4-phenylpyridinium; 73-31-4/Melatonin; EC 2.7.11.22/Cyclin-Dependent Kinase 5; EC 3.4.22.-/Calpain; EC 3.4.22.-/Casp3 protein, rat; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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