α1整合素活化在β淀粉樣蛋白誘導(dǎo)神經(jīng)細(xì)胞死亡中的作用
發(fā)布時(shí)間:2018-03-15 10:03
本文選題:整合素 切入點(diǎn):黏著斑激酶 出處:《中國老年學(xué)雜志》2017年18期 論文類型:期刊論文
【摘要】:目的探討神經(jīng)母細(xì)胞瘤細(xì)胞(SH-SY5Y)中β淀粉樣蛋白(Aβ)誘導(dǎo)絲裂原活化蛋白激酶(MAPK)信號(hào)通路活化的上游影響因素。方法選擇SH-SY5Y為靶細(xì)胞,首先用MAPK信號(hào)通路上游抑制劑處理細(xì)胞,待細(xì)胞培養(yǎng)1 h之后,加入Aβ42纖維聚集體,細(xì)胞培養(yǎng)24 h后進(jìn)行檢測。首先采用甲氮甲唑藍(lán)(MTT)法測定了細(xì)胞的存活率,然后利用Western印跡檢測磷酸化細(xì)胞外信號(hào)調(diào)節(jié)蛋白激酶(p-ERK)和ERK的蛋白表達(dá)水平,從而檢測MAPK信號(hào)通路的激活水平。結(jié)果用鋸鱗血抑肽或α1整合素蛋白封閉性抗體可以有效抑制Aβ引起的細(xì)胞死亡,并且阻止Aβ成纖維誘導(dǎo)MAPK的激活水平的提高(P0.05)。用α1和β1整合素蛋白封閉抗體同時(shí)作用細(xì)胞時(shí),得到了相似的結(jié)果。但是如果只用β1整合素蛋白封閉抗體單獨(dú)作用細(xì)胞時(shí),不能阻止Aβ成纖維誘導(dǎo)細(xì)胞死亡和MAPK的激活水平的提高。結(jié)論α1整合素,α1和β1整合素復(fù)合體是Aβ誘導(dǎo)SH-SY5Y細(xì)胞中MAPK信號(hào)通路激活從而介導(dǎo)細(xì)胞死亡的重要因素。推測α1整合素蛋白和α1、β1復(fù)合體可以作為治療性干擾Aβ信號(hào)通路的靶點(diǎn)。
[Abstract]:Objective to investigate the upstream effects of 尾 -amyloid protein A 尾 on mitogen-activated protein kinase (MAPK) signal pathway activation in neuroblastoma cell line SH-SY5Y.Methods SH-SY5Y was selected as target cell and MAPK signal pathway upstream inhibitor was used to treat cells. After the cells were cultured for 1 hour, A 尾 42 fiber aggregates were added, and the cells were cultured for 24 h. The survival rate of the cells was determined by methazolyl methazolyl methionine (MTT) method. Then Western blot was used to detect the expression of phosphorylated signal regulated protein kinase p-ERK (p-ERK) and ERK. The activation level of MAPK signaling pathway was detected. Results A 尾 -induced cell death could be effectively inhibited by anti-peptide or 偽 1 integrin protein blocking antibody. The same results were obtained when 偽 1 and 尾 1 integrin protein blocked the cells simultaneously. However, if only 尾 1 integrin protein blocked the cells, but only 尾 1 integrin protein blocked the cells alone. Conclusion 偽 _ 1 integrin, 偽 _ 1 and 尾 _ 1 integrin complexes are important factors for the activation of MAPK signaling pathway in A 尾 -induced SH-SY5Y cells and thus mediates cell death. 偽 1 integrin protein and 偽 1, 尾 1 complex can be used as targets for therapeutic interference of A 尾 signaling pathway.
【作者單位】: 鄭州大學(xué)附屬南陽醫(yī)院南陽市中心醫(yī)院神經(jīng)外科;
【分類號(hào)】:R749.16
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本文編號(hào):1615543
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