贵州医科大学学报

2017, v.42;No.198(03) 253-257

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Aβ_(1-42)寡聚体在非Caspase依赖性细胞凋亡通路中的作用机制
Study on the Mechanism of Aβ_(1-42) Oligomers in Caspase-independent Apoptosis Pathway

杨梅;任真奎;官志忠;禹文峰;
YANG Mei;REN Zhenkui;GUAN Zhizhong;YU Wenfeng;Key Laboratory of Medical Molecular Biology,Guizhou Medical University;Key Laboratory of Endemic and Ethnic Diseases,Ministry of Education,Guizhou Medical University;Department of Pathology,Guizhou Medical University;

摘要(Abstract):

目的:观察Aβ_(1-42)寡聚体对凋亡诱导因子(AIF)在神经细胞线粒体或细胞核中表达的影响。方法:将体外培养原代神经细胞分为对照组和Aβ_(1-42)寡聚体处理组,(分别用0.1、0.2、0.5及1μmol/L的Aβ_(1-42)寡聚体处理24 h),采用MTT法测定神经细胞的相对生存率,Western blotting检测凋亡诱导因子(AIF)在神经细胞的线粒体和细胞核中的表达。结果:MTT结果显示,与对照组比较,Aβ_(1-42)寡聚体处理组的OD值均有不同程度的下降,Aβ_(1-42)寡聚体为0.1、0.2及0.5μmol/L时的细胞相对生存率明显降低(P<0.05),1μmol/L时降低最明显(P<0.01);与对照组比较,Aβ_(1-42)寡聚体处理组神经细胞线粒体中AIF蛋白表达减少(P<0.05或P<0.01),而细胞核中AIF蛋白表达升高(P<0.05或P<0.01)。结论:Aβ_(1-42)寡聚体可能通过AIF介导的非Caspase依赖性细胞凋亡通路导致大鼠神经细胞的凋亡,其机制可能与Aβ_(1-42)寡聚体促进AIF从线粒体向细胞核转移有关。
Objective:To investigate the mechanism of expression of Aβ_(1-42) oligomers on AIF in mitochondrion or nucleus. Methods:Cortical neuronal cultures were divided into control and Aβ_(1-42) oligomers group. Aβ_(1-42) oligomers were prepared using chemically synthetic Aβ_(1-42) in vitro( treated by0. 1,0. 2,0. 5,1. 0μmol/L Aβ_(1-42) oligomers for 24h),and detected relative survival rate of neuronal cells by MTT. Western blotting was used to detect the expression of AIF in neuronal mitochondria and nucleus. Results:MTT indicated that OD value of Aβ_(1-42) oligomers treated group showed decrease in various degree comparing with control group; with the Aβ_(1-42) oligomers as 0. 1,0. 2 and 0. 5 μmol/L,relative survival rate of cells were obviously lowered( P < 0. 05),while at 1 μmol/L reached the most obvious decrease( P < 0. 01); the protein level of AIF in the mitochondria of Aβ_(1-42) oligomers group was significantly lower compared to control group( P < 0. 05 or P < 0. 01),while the protein level of AIF in the nucleus was significantly increased( P < 0. 05 or P < 0. 01). Conclusion:It is possible that Aβ_(1-42) oligomers caused apoptosis of rats neuronal cell via AIF induced Caspase independent cell apoptosis pathway. The mechanism is possible to be relevant with Aβ_(1-42) oligomers enhancing AIF translocation from mitochondrial to nuclear.

关键词(KeyWords): 细胞凋亡;阿尔茨海默病;细胞;神经;大鼠,Sprague-Dawley;凋亡诱导因子;Aβ1-42寡聚体
cell apoptosis;Alzheimer’s disease;cells;neuron;rats,Sprague-Dawley;apoptosis-inducing factor;Aβ1-42 oligomers

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Keywords:

基金项目(Foundation): 国家自然科学基金(81360199);; 教育部科学技术研究项目(213032A);; 贵州省国际科技合作计划项目[黔科合外G字(2013)7026];; 贵州省创新计划项目[黔教合协同创新中心(2014)06];; 贵州省教育厅项目(2015年贵州省普通高等学校地方病和少数民族疾病防控创新团队);; 贵州省科技厅计划课题[黔科合重大专项字(2014)6008]

作者(Author): 杨梅;任真奎;官志忠;禹文峰;
YANG Mei;REN Zhenkui;GUAN Zhizhong;YU Wenfeng;Key Laboratory of Medical Molecular Biology,Guizhou Medical University;Key Laboratory of Endemic and Ethnic Diseases,Ministry of Education,Guizhou Medical University;Department of Pathology,Guizhou Medical University;

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DOI: 10.19367/j.cnki.1000-2707.2017.03.002

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