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Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP(+)-induced human neuroblastoma SH-SY5Y cell death.
MedLine Citation:
PMID:  22265823     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
In an attempt to clarify the protective effect of puerarin on toxin-insulted dopaminergic neuronal death, this present study was carried out by using a typical Parkinson's disease (PD) model - 1-methyl-4-phenylpyridinium iodide (MPP(+))-induced dopaminergic SH-SY5Y cellular model. Data are presented, which showed that puerarin up-regulated Akt phosphorylation in both of MPP(+)-treated and non-MPP(+)-treated cells. The presence of PI3K inhibitor LY294002 completely blocked puerarin-induced activation of Akt phosphorylation. Moreover, puerarin decreased MPP(+)-induced cell death, which was blocked by phosphoinositide 3-kinase (PI3K) inhibitor LY294002. We further demonstrated that puerarin protected against MPP(+)-induced p53 nuclear accumulation, Puma (p53-upregulated mediator of apoptosis) and Bax expression and caspase-3-dependent programmed cell death (PCD). This protection was blocked by applying a PI3K/Akt inhibitor. Additionally, it was Pifithrin-α, but not Pifithrin-μ, which blocked MPP(+)-induced Puma and Bax expression, caspase-3 activation and cell death. Collectively, these data suggest that the activation of PI3K/Akt pathway is involved in the protective effect of puerarin against MPP(+)-induced neuroblastoma SH-SY5Y cell death through inhibiting nuclear p53 accumulation and subsequently caspase-3-dependent PCD. Puerarin might be a potential therapeutic agent for PD.
Authors:
Guoqi Zhu; Xuncui Wang; Shengbing Wu; Qinglin Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-12
Journal Detail:
Title:  Neurochemistry international     Volume:  -     ISSN:  1872-9754     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8006959     Medline TA:  Neurochem Int     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Affiliation:
Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei 230038, China.
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