摘要
目的研究P38 MAPK信号通路的激活对SH-SY5Y细胞内β-淀粉样肽(Aβ)生成的影响。方法 P38 MAPK信号通路激动剂茴香霉素处理神经母细胞瘤(SH-SY5Y)细胞1和72 h,ELISA方法检测细胞内Aβ含量;实时定量PCR和Western blot分别检测APP、PS1和BACE1基因mRNA和蛋白的表达。结果经茴香霉素处理1和72 h的SH-SY5Y细胞磷酸化的P38 MAPK表达均明显增加;茴香霉素处理72 h后细胞内Aβ1-40含量约为(46.88±3.60)pg/mL,对照组为(39.09±1.60)pg/mL(P<0.05);茴香霉素处理1 h后细胞内APP和PS1mRNA表达明显增多,而处理72 h后APP、PS1和BACE1mRNA表达均明显增多;茴香霉素处理1 h后细胞内APP、PS1和BACE1蛋白表达无明显改变,而处理72 h后APP、PS1和BACE1蛋白表达均明显增多,分别为对照组的1.45倍、1.38倍和1.60倍。结论 P38 MAPK信号通路的激活可促使Aβ生成增加,在阿尔茨海默病的发病过程中起一定作用。
Objective To investigate the effect of the activation of P38 MAPK signaling pathway on the intracellular β-amyloid（Aβ） production in human neuroblastoma SH-SY5Y.Methods SH-SY5Y cells were used to test intracellular Aβ levels by ELISA after activation of P38 MAPK signaling pathway by anisomycin for 1 and 72 h.The mRNA and protein levels of APP,PS1 and BACE1 were examined by RT-PCR and Western blot respectively.Results The expression of Phospho-P38 MAPK was increased after anisomycin treatment for 1 and 72 h;the production of Aβ1-40 was about（46.88±3.60） pg/mL[Control group was（39.09±1.60） pg/mL,P0.05]after anisomycin treatment for 72 h;APP and PS1 mRNA was increased after anisomycin treatment for 1 h,while APP,PS1 and BACE1 mRNA was significantly increased after anisomycin treatment for 72 h;the protein levels of APP,PS1 and BACE1 were increased as 1.45-fold,1.38-fold and 1.60-fold respectively as control after anisomycin treatment for 72 h while nothing alter for 1 h.Conclusion Activation of P38 MAPK signaling pathway may increase Aβ production and play a role in the pathogensis of Alzheimer＇s disease（AD）.
出处
《基础医学与临床》
CSCD
北大核心
2011年第6期683-687,共5页
Basic and Clinical Medicine
基金
北京市自然科学基金(7102012)
北京市教育委员会科技计划基金(KM201110025006)
