| Protective activity of guanosine in an in vitro model of Parkinson's disease. | |
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MedLine Citation:
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PMID: 23138720 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: JOURNAL ARTICLE Date: 2012-11-09 |
Journal Detail:
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Title: Panminerva medica Volume: - ISSN: 1827-1898 ISO Abbreviation: Panminerva Med Publication Date: 2012 Nov |
Date Detail:
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Created Date: 2012-11-9 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0421110 Medline TA: Panminerva Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Experimental and Clinical Sciences University of Chieti-Pescara, Chieti, Italy - p.ballerini@unich.it. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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