Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP+-induced human neuroblastoma SH-SY5Y cell death
- 作者：Guoqi Zhu ; Xuncui Wang ; Shengbing Wu ; Qinglin Li ; qinglin_lee@hotmail.com
- 关键词：PD ; Parkinson&rsquo ; s disease ; GSK3尾 ; glycogen synthase kinase-3尾 ; PI3K ; phosphoinositide 3-kinase ; SN ; Substantia Nigra ; ROS ; reactive oxidative species ; MPP+ ; 1-methyl-4-phenylpyridinium iodide
- 刊名：Neurochemistry International
- 出版年：2012
- 期刊代码：120_01970186
- 类别：bio
- 出版时间：March, 2012
- 卷：60
- 期：4
- 页码：400-408
- 文件大小：891 K
摘要
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鈥檚 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-伪, but not Pifithrin-渭, 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.