原花青素对Aβ25-35介导的tau蛋白过度磷酸化及p38MAPK信号通路的影响

doi:10.3969/j.issn.1004-616x.2019.02.002

Abstract

Abstract: OBJECTIVE:To investigate the influence of proanthocyanidin on amyloid β-peptide (25-35)(Aβ_25-35)-mediated tau hyperphosphorylation and p38 MAPK pathway signaling in SH-SY5Y cells.METHODS:SH-SY5Y cells were exposed to 1.0 μmol/L Aβ_25-35 to establish an Alzheimer's disease (AD) model in vitro.The study involved,a control group (cells and medium only),Aβ_25-35 intervention group,Aβ_25-35+different concentrations (0.1,1.0,2.5,5.0 μg/mL) of proanthocyanidin treatment group and p38 pathway blocker SB203580 group,Aβ_25-35+SB203580 group,Aβ_25-35+5.0 μg/mL proanthocyanidin intervention group.MTT assay was used to detect vitality of SH-SY5Y cells.Content of MDA in the cells was detected by TBA method and the total level of SOD was detected by WST-1 method.Expression of p-tau,tau,p38,p-p38 protein and p-tau,tau,p38,p-p38 levels after p38 pathway blocker were detected by Western blot analysis.RESULTS:Proanthocyanidin showed no obvious toxic effects on SH-SY5Y cells but,different concentrations of Aβ_25-35 decreased the survival rate of these cells.Compared with the control group,the level of SOD was decreased in 1.0 μmol/L Aβ_25-35 group,the content of MDA was increased (P < 0.05) and the expression of p-tau (Ser396) and p-p38 protein was also increased (P < 0.05).After the intervention with different concentrations of proanthocyanidin and p38 signaling pathway blocker,and compared with the 1.0 μmol/L Aβ_25-35 group,PC inhibited the expression levels of p-tau (Ser396) and p-p38 protein (P < 0.05),improved the vitality of SH-SY5Y cells and the total SOD level,Moreover,the MDA content was decreased (P < 0.05),and Aβ+blocker group down-regulated protein expression levels (P < 0.05).CONCLUSION:Proanthocyanidin inhibited hyper-phosphorylation of tau protein which was mediated by Aβ_25-35,improved the vitality of cells and reduced oxidative stress level.In addition,the inhibitory effect of proanthocyanidin on p38MAPK signaling pathway was of great significance to neuroprotection by inhibiting the hyperphosphorylation of tau protein.

Key words: proanthocyanidins, Aβ_25-35, tau protein, p38MAPK

CLC Number:

R994.6

WANG Xu, ZHANG Xiaoqiang, LIU Jing, CHEN Yaoyao, LU Xiaoxing, MIAO Xinyu. Influence of proanthocyanidin on amyloid[β]-peptide(25-35)-mediated tau hyperphosphorylation and p38 MAPK pathway signaling in SH-SY5Y cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(2): 96-101,110.

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Influence of proanthocyanidin on amyloid[β]-peptide(25-35)-mediated tau hyperphosphorylation and p38 MAPK pathway signaling in SH-SY5Y cells

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