Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP+-induced human neuroblastoma SH-SY5Y cell death

• Published in: Neurochemistry international Vol. 60; no. 4; pp. 400 - 408
• Main Authors: Zhu, Guoqi, Wang, Xuncui, Wu, Shengbing, Li, Qinglin
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01-03-2012; Elsevier
• Subjects: 1-Methyl-4-phenylpyridinium - toxicity; Apoptosis - drug effects; Base Sequence; Biological and medical sciences; Caspase-3; Cell Line, Tumor; DNA Primers; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Humans; Immunohistochemistry; Isoflavones - pharmacology; Neuroblastoma - enzymology; Neuroblastoma - pathology; Neuroblastoma - prevention & control; p53; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt pathway; Proto-Oncogene Proteins c-akt - metabolism; Puerarin; Reverse Transcriptase Polymerase Chain Reaction; Vertebrates: nervous system and sense organs; GSK3β; PI3K/Akt pathway; PD; PI3K; ROS; SN; MPP; Puerarin; Caspase-3; p53; Human; Enzyme; Cysteine endopeptidases; p53 Protein; Caspase; Peptidases; Cell line; Neuron; Cell death; Hydrolases
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2012.01.003

► Puerarin prevents against MPP+-induced cell death through PI3K/Akt signal pathway. ► Puerarin-activated PI3K/Akt signal pathway blocks MPP+-induced p53 nuclear accumulation. ► Puerarin protects against MPP+-induced cell death through p53-mediated Puma, Bax and caspase-3 dependent apoptosis.
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.