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Protective activity of guanosine in an in vitro model of Parkinson's disease.
MedLine Citation:
PMID:  23138720     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Parkinson's disease (PD) is a pathological condition characterized by a progressive neurodegeneration of dopaminergic neurons with the consequent reduction of dopamine content in the substantia nigra. The neurotoxin 6-hydroxydopamine (6-OHDA) is widely used to mimic the neuropathology of PD in both in vivo and in vitro experimental models. We found that, as expected, in dopaminergic human SH-SY5Y neuroblastoma cells the toxin reduced cell viability causing programmed cell death as assessed by an increase in DNA fragmentation. We also examined, in these cells, the activation/inactivation of several pro and anti apoptotic signaling pathways by 6-OHDA including p-38 kinase (p-38), c-Jun N-terminal kinase (JNK), protein kinase B (also known as Akt), glycogen synthase kinase-3β (GSK3β), and Bcl-2 protein. Guanine-based purines, exert neuroprotective effects and we previously reported that guanosine activates cell survival pathways including PI3K/Akt/PKB signaling in different kinds of cells including glia and neuroblastoma cells. In the present study we found that guanosine (300 µM) protected SH-SY5Y neuroblastoma cells when they were exposed to 6-OHDA, promoting their survival. Guanosine reduced the 6-OHDA mediated activation of p-38 and JNK. Moreover the nucleoside potentiated the early increase in the phosphorylation of the anti-apoptotic kinase Akt and the increase in the expression of the anti-apoptotic Bcl-2 protein induced by 6-OHDA. In summary our results show that guanosine results to be neuroprotective in a recognized in vitro model of PD thus suggesting that it could represent a new potential pharmacological tool to be studied in the therapeutic approach to PD.
Authors:
P P Giuliani; S S Romano; P P Ballerini; R R Ciccarelli; N N Petragnani; S S Cicchitti; M M Zuccarini; S Jiang; Mp Rathbone; F Caciagli; P Di Iorio
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-09
Journal Detail:
Title:  Panminerva medica     Volume:  -     ISSN:  1827-1898     ISO Abbreviation:  Panminerva Med     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0421110     Medline TA:  Panminerva Med     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Experimental and Clinical Sciences University of Chieti-Pescara, Chieti, Italy - p.ballerini@unich.it.
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