本文選題：阿爾茨海默病　切入點：Tau　出處：《貴州醫(yī)科大學》2017年碩士論文

【摘要】：目的:研究α7尼古丁受體(n ACh R)拮抗或基因沉默對SH-SY5Y細胞Tau蛋白S404和S214位點磷酸化水平的影響及其與p38 MAPK通路的關系,探討α7 n ACh R調節(jié)Tau蛋白位點磷酸化的相關機制。方法:用α7 n ACh R拮抗劑MLA、p38 MAPK通路阻滯劑SB203580及通路激動劑Anisomycin分別或聯合處理SH-SY5Y細胞。用Real-time PCR法和Western blotting法分別測定沉默細胞中α7 n ACh R在m RNA和蛋白質表達水平的變化;Western blotting方法測定細胞Tau蛋白、p-Tau(S404)、p-Tau(S214)、p38 MAPK及p-p38 MAPK(Thr180/Tyr182)蛋白水平。結果:α7 n ACh R沉默組與空質粒組相比,α7 n ACh R m RNA和蛋白質水平分別降低了91%(P0.01)和80%(P0.01);p-Tau(S404)蛋白水平升高了71%(P0.01),p-Tau(S214)蛋白水平升高了73%(P0.01),p-p38蛋白水平升高了65%(P0.01)。此外,Anisomycin與MLA、SB203580與MLA、單獨MLA處理組共同檢測Tau蛋白S404和S214位點磷酸化水平及通路蛋白表達情況,結果顯示,MLA處理組和Anisomycin與MLA共同處理組均引起p-Tau(S404)、p-Tau(S214)及p-p38 MAPK蛋白水平明顯升高(P0.01),SB203580與MLA共同處理組引起p-Tau(S404)、p-Tau(S214)和p-p38 MAPK蛋白水平顯著降低(P0.01)。結論:α7 n ACh R基因沉默或受體拮抗可導致Tau蛋白S404和S214位點磷酸化水平升高并激活p38 MAPK信號通路;抑制p38 MAPK信號轉導通路可使MLA誘導的Tau蛋白S404和S214位點磷酸化水平顯著降低。
[Abstract]:Aim: to investigate the effects of 偽 7 nicotine receptor n ACh R antagonism or gene silencing on the phosphorylation of S404 and S214 sites of Tau protein in SH-SY5Y cells and its relationship with p38 MAPK pathway, and to explore the mechanism of 偽 7 n ACh R regulating the phosphorylation of Tau protein sites.Methods: SH-SY5Y cells were treated with 偽 7 n ACh R antagonist MLAA p38 MAPK pathway blocker SB203580 and pathway agonist Anisomycin, respectively.The expression of 偽 7 n ACh R in m RNA and protein was measured by Real-time PCR assay and Western blotting method. The protein levels of Tau protein p-Taun S404 and p-p38 MAPKtr 180 / Tyr182 were measured by Real-time PCR and Western blotting.In addition, Anisomycin and MLA-SB203580 and MLA-treated group were used to detect the phosphorylation level of Tau protein S404 and S214 and the expression of pathway protein.Conclusion: 偽 7n ACh R gene silencing or receptor antagonism can increase the phosphorylation level of S404 and S214 sites of Tau protein and activate p38 MAPK signaling pathway, and inhibit the phosphorylation level of Tau protein S404 and S214 sites induced by MLA.
【學位授予單位】：貴州醫(yī)科大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R749.16

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相關期刊論文 前2條

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