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

癌变·畸变·突变 ›› 2019, Vol. 31 ›› Issue (2): 96-101,110.doi: 10.3969/j.issn.1004-616x.2019.02.002

原花青素对Aβ_25-35介导的tau蛋白过度磷酸化及p38MAPK信号通路的影响

王旭^1,2, 张小强^1,2, 刘静^1,2, 陈姚姚^1,2, 卢晓星^1,2, 苗歆雨^1,2

1. 东南大学公共卫生学院, 江苏南京 210009;
2. 东南大学环境医学工程教育部重点实验室, 江苏南京 210009

收稿日期:2018-10-11 修回日期:2019-03-07 出版日期:2019-03-30 发布日期:2019-03-30
通讯作者: 张小强,E-mail:zhangxq7843@126.com E-mail:zhangxq7843@126.com
作者简介:王旭,E-mail:wangxu920526@163.com
基金资助:
中央高校基本科研业务费专项资金；江苏省普通高校研究生科研创新计划项目（SJCX17_0071）

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

WANG Xu^1,2, ZHANG Xiaoqiang^1,2, LIU Jing^1,2, CHEN Yaoyao^1,2, LU Xiaoxing^1,2, MIAO Xinyu^1,2

1. School of Public Health, Southeast University, Nanjing 210009;
2. Key Laboratory of Environmental Medicine, Engineering of Ministry of Education, Southeast University, Nanjing 210009, Jiangsu, China

Received:2018-10-11 Revised:2019-03-07 Online:2019-03-30 Published:2019-03-30

摘要/Abstract

摘要： 目的：研究原花青素对β-淀粉样蛋白25-35片段（Aβ_25-35）介导SH-SY5Y细胞tau蛋白过度磷酸化及p38 MAPK信号通路的抑制作用。方法：采用1.0 μmol/L的Aβ_25-35诱导SH-SY5Y细胞建立体外阿尔茨海默病（AD）模型，并分别设立对照组（只含细胞和培养基）、Aβ_25-35染毒组、Aβ_25-35+不同浓度（0.1、1.0、2.5、5.0 μg/mL）的原花青素处理组以及p38通路阻断剂SB203580组、Aβ_25-35+SB203580组、Aβ_25-35+5.0 μg/mL原花青素干预组。四甲基噻唑蓝（MTT）法检测SH-SY5Y细胞存活率，TBA法检测细胞内MDA含量，WST-1法检测细胞内总SOD水平，Western blot法检测p-tau、tau蛋白的表达及应用p38通路阻断剂后p-tau、tau、p38、p-p38相应的蛋白表达。结果：原花青素对SH-SY5Y细胞无明显毒性作用，不同浓度Aβ_25-35均使SH-SY5Y细胞存活率降低，与对照组比较，1.0 μmol/L Aβ_25-35组SOD水平降低，MDA含量升高（P < 0.05），p-tau （Ser396）和p-p38蛋白表达亦增加（P < 0.05）；给予不同浓度原花青素干预及p38通路阻断剂后，与1.0 μmol/L Aβ_25-35组比较，原花青素提高SH-SY5Y细胞生存率及细胞内总SOD水平，降低细胞内MDA含量（P均<0.05），抑制Aβ_25-35介导的p-tau （Ser396）和p-p38蛋白过度表达（P均<0.05），且Aβ+阻断剂组同样抑制相关蛋白的表达水平（P均<0.05）。结论：原花青素能够抑制Aβ_25-35介导的tau蛋白过度磷酸化，提高细胞生存率，降低氧化应激水平。此外，原花青素可通过抑制p38 MAPK信号传导途径来实现其抑制tau蛋白过度磷酸化的神经保护作用。

关键词: 原花青素, Aβ_25-35, tau蛋白, p38MAPK

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

中图分类号:

R994.6

王旭, 张小强, 刘静, 陈姚姚, 卢晓星, 苗歆雨. 原花青素对Aβ_25-35介导的tau蛋白过度磷酸化及p38MAPK信号通路的影响[J]. 癌变·畸变·突变, 2019, 31(2): 96-101,110.

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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原花青素对Aβ_25-35介导的tau蛋白过度磷酸化及p38MAPK信号通路的影响

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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