SH-SY5Y细胞α7尼古丁受体蛋白抑制对tau蛋白及p38 MAPK通路的影响及其与AD发病机制的关系  

Influence of inhibited α7 nicotinic acetylcholine receptor protein expression on tau protein and p38 MAPK signal transduction pathway in SH-SY5Y cells and the relationship with the pathogenesis of AD

作　　者：周飞[1] 李毅[1] 吴昌学[1] 官志忠[1] 齐晓岚[1] 

机构地区：[1]贵州医科大学分子生物学重点实验室贵州医科大学地方病与少数民族性疾病教育部重点实验室,贵州贵阳550004

出　　处：《中风与神经疾病杂志》2017年第2期137-140,共4页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金资助项目(81360178);教育部"长江学者和创新团队发展计划资助"(IRT13058);贵州省科技厅重大专项[黔科合重大专项字2014(6008)];贵州省科技厅项目[201344;黔科合SY字(2013)][3020黔科合LH字(2016)7365]

摘　　要：目的研究α7尼古丁受体(nAChR)蛋白抑制对SH-SY5Y细胞tau蛋白磷酸化水平的影响及其与p38 MAPK通路的关系,探讨α7 nAChR调节tau蛋白磷酸化的相关机制。方法用α7 nAChR阻断剂MLA阻断SH-SY5Y细胞α7 nAChR蛋白的活化及其表达,用p38 MAPK阻断剂SB203580阻断SH-SY5Y细胞p38 MAPK信号通路蛋白的活化及其表达,Western blotting方法测定tau蛋白、p-tau(S404)、p-tau(S214)、α7 nAChR、p38 MAPK及p-p38 MAPK(Thr180/Tyr182)蛋白表达水平。结果细胞经MLA处理后,p-tau(S404)和p-tau(S214)蛋白水平明显升高(P<0.01),p-p38 MAPK和α7 nAChR蛋白水平明显降低(P<0.01),tau蛋白和p38 MAPK蛋白水平保持不变;经SB203580处理后,SB203580及MLA共同处理后均引起p-tau(S404)、p-tau(S214)、p-p38 MAPK和α7nAChR蛋白水平显著降低(P<0.01),tau蛋白和p38 MAPK蛋白水平无变化。结论α7 nAChR可通过阻断p38MAPK信号传导通路抑制tau蛋白过度磷酸化。Objective To investigate the influence of inhibited protein expression of α7 neuronal nicotinic acetyl-choline receptor （nAChR） on tau phosphorylation and the relationship with p38 MAPK signal transduction pathway in SH- SY5Y cells,to study the effected mechanism of al nAChR on tau phosphorylation. Methods SH-SY5Y cells were exposed to MLA and SB203580,respectively,to block the activation and protein expression of α7 nAChR and p38 MAPK pathway. The protein levels of tau,p-tau （S404） ,p-tau （S214） ,a7 nAChR,p38 MAPK and p-p38 MAPK （Thrl80/Tyrl82） were measured by Western blotting. Results As compared with negative controls,in MLA treated group,the expressions of p-tau （S404） and p-tau （S214） were increased and the protein levels of α7 nAChR and p-p38 MAPK were decreased signifi-cantly, tau and p38 MAPK protein expressions were unchanged. In SB203580 treated group and both two medicines treated group, the expressions of p-tau （S404）, p-tau （S214）,a7 nAChR and p-p38 MAPK were both decreased conspicuously, the protein levels of tau and p38 MAPK were still unchanged. Conclusions Blocked p38 MAPK signal transduction pathway can prevent against the al nAChR-induced tau hyperphosphorylation.

关 键 词：阿尔茨海默病 tau α7 NACHR p38 MAPK 

分 类 号：R749.01[医药卫生—神经病学与精神病学]