| pubmed-article:18404453 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:18404453 | lifeskim:mentions | umls-concept:C0815000 | lld:lifeskim |
| pubmed-article:18404453 | lifeskim:mentions | umls-concept:C0596402 | lld:lifeskim |
| pubmed-article:18404453 | lifeskim:mentions | umls-concept:C0018330 | lld:lifeskim |
| pubmed-article:18404453 | lifeskim:mentions | umls-concept:C1417248 | lld:lifeskim |
| pubmed-article:18404453 | lifeskim:mentions | umls-concept:C0680242 | lld:lifeskim |
| pubmed-article:18404453 | lifeskim:mentions | umls-concept:C0205263 | lld:lifeskim |
| pubmed-article:18404453 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:18404453 | pubmed:dateCreated | 2008-4-11 | lld:pubmed |
| pubmed-article:18404453 | pubmed:abstractText | Guanosine exerts neuroprotective effects in the central nervous system. Apoptosis, a morphological form of programmed cell death, is implicated in the pathophysiology of Parkinson's disease (PD). MPP(+), a dopaminergic neurotoxin, produces in vivo and in vitro cellular changes characteristic of PD, such as cytotoxicity, resulting in apoptosis. Undifferentiated human SH-SY5Y neuroblastoma cells had been used as an in vitro model of Parkinson's disease. We investigated if extracellular guanosine affected MPP(+)-induced cytotoxicity and examined the molecular mechanisms mediating its effects. Exposure of neuroblastoma cells to MPP(+) (10 muM-5 mM for 24-72 h) induced DNA fragmentation in a time-dependent manner (p < 0.05). Administration of guanosine (100 muM) before, concomitantly with or, importantly, after the addition of MPP(+) abolished MPP(+)-induced DNA fragmentation. Addition of MPP(+) (500 muM) to cells increased caspase-3 activity over 72 h (p < 0.05), and this was abolished by pre- or co-treatment with guanosine. Exposure of cells to pertussis toxin prior to MPP(+) eliminated the anti-apoptotic effect of guanosine, indicating that this effect is dependent on a Gi protein-coupled receptor, most likely the putative guanosine receptor. The protection by guanosine was also abolished by the selective inhibitor of the enzyme PI-3-K/Akt/PKB (LY294002), confirming that this pathway plays a decisive role in this effect of guanosine. Neither MPP(+) nor guanosine had any significant effect on alpha-synuclein expression. Thus, guanosine antagonizes and reverses MPP(+)-induced cytotoxicity of neuroblastoma cells via activation of the cell survival pathway, PI-3-K/Akt/PKB. Our results suggest that guanosine may be an effective pharmacological intervention in PD. | lld:pubmed |
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| pubmed-article:18404453 | pubmed:language | eng | lld:pubmed |
| pubmed-article:18404453 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:18404453 | pubmed:status | PubMed-not-MEDLINE | lld:pubmed |
| pubmed-article:18404453 | pubmed:month | Sep | lld:pubmed |
| pubmed-article:18404453 | pubmed:issn | 1573-9538 | lld:pubmed |
| pubmed-article:18404453 | pubmed:author | pubmed-author:WerstiukEva... | lld:pubmed |
| pubmed-article:18404453 | pubmed:author | pubmed-author:RathboneMiche... | lld:pubmed |
| pubmed-article:18404453 | pubmed:author | pubmed-author:JiangShucuiS | lld:pubmed |
| pubmed-article:18404453 | pubmed:author | pubmed-author:BalleriniPatr... | lld:pubmed |
| pubmed-article:18404453 | pubmed:author | pubmed-author:D'AlimonteIol... | lld:pubmed |
| pubmed-article:18404453 | pubmed:author | pubmed-author:PettiferKathl... | lld:pubmed |
| pubmed-article:18404453 | pubmed:author | pubmed-author:BauChristianC | lld:pubmed |
| pubmed-article:18404453 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:18404453 | pubmed:volume | 3 | lld:pubmed |
