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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.
Neurochem Int. 2012 Mar; 60(4):400-8.NI

Abstract

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+Show Affiliations

Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei, China.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22265823

Citation

Zhu, Guoqi, et al. "Involvement of Activation of PI3K/Akt Pathway in the Protective Effects of Puerarin Against MPP+-induced Human Neuroblastoma SH-SY5Y Cell Death." Neurochemistry International, vol. 60, no. 4, 2012, pp. 400-8.
Zhu G, Wang X, Wu S, et al. Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP+-induced human neuroblastoma SH-SY5Y cell death. Neurochem Int. 2012;60(4):400-8.
Zhu, G., Wang, X., Wu, S., & Li, Q. (2012). Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP+-induced human neuroblastoma SH-SY5Y cell death. Neurochemistry International, 60(4), 400-8. https://doi.org/10.1016/j.neuint.2012.01.003
Zhu G, et al. Involvement of Activation of PI3K/Akt Pathway in the Protective Effects of Puerarin Against MPP+-induced Human Neuroblastoma SH-SY5Y Cell Death. Neurochem Int. 2012;60(4):400-8. PubMed PMID: 22265823.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP+-induced human neuroblastoma SH-SY5Y cell death. AU - Zhu,Guoqi, AU - Wang,Xuncui, AU - Wu,Shengbing, AU - Li,Qinglin, Y1 - 2012/01/12/ PY - 2011/11/09/received PY - 2011/12/28/revised PY - 2012/01/04/accepted PY - 2012/1/24/entrez PY - 2012/1/24/pubmed PY - 2012/7/6/medline SP - 400 EP - 8 JF - Neurochemistry international JO - Neurochem Int VL - 60 IS - 4 N2 - 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. SN - 1872-9754 UR - https://www.unboundmedicine.com/medline/citation/22265823/Involvement_of_activation_of_PI3K/Akt_pathway_in_the_protective_effects_of_puerarin_against_MPP+_induced_human_neuroblastoma_SH_SY5Y_cell_death_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0197-0186(12)00004-6 DB - PRIME DP - Unbound Medicine ER -