摘要
目的研究P38MAPK信号通路的激活对淀粉前体蛋白(APP)表达的影响及其相关表观遗传学机制。方法体外培养神经母细胞瘤细胞(SH-SY5Y),Western blot法检测SH-SY5Y的APP蛋白表达及组蛋白乙酰化酶(HAT)和组蛋白去乙酰化酶(HDAC)的表达;吸光度值法检测组蛋白3(H3)和组蛋白4(H4)整体乙酰化水平。结果 P38MAPK信号通路经特异性激动剂激活SH-SY5Y 72 h后,APP表达明显增高至对照组的1.5倍(0.41±0.09vs0.28±0.08,P<0.01);同时组蛋白H3整体乙酰化水平增高(0.20±0.04vs0.06±0.03,P<0.01),但H4乙酰化水平无明显改变;组蛋白乙酰化酶CBP表达增高至对照组的2.5倍(0.30±0.03vs0.11±0.05,P<0.01),而组蛋白去乙酰化酶HDAC3表达下降至对照组的40%(0.19±0.05vs0.49±0.03,P<0.01)。结论 P38MAPK信号通路可能通过上调组蛋白乙酰化水平增加SH-SY5Y的APP蛋白表达。
Objective To investigate the role of P38MAPK in the expression of β-Amyloid precursor protein（APP） and it＇s epigenetic mechanisms.Methods Cultured SH-SY5Y cells were used to test the expression of APP,histone acetyltranferase（HAT） and histone deacetyltranferase（HDAC） by Western blot after activation of P38MAPK;Acetylation level of histone H3 and H4 were examined by optical density assay.Results APP expression was increased after P38MAPK activation for 72 hours compared to the control（0.41±0.09 vs 0.28±0.08,P〈0.01）.Level of histone H3 acetylation was increased（0.20±0.04 vs 0.06±0.03,P〈0.01）accompanied with up-regulation of CBP（0.30±0.03 vs 0.11±0.05,P〈0.01） and down-regulation of HDAC3（0.19±0.05 vs 0.49±0.03,P〈0.01）.Conclusion APP expression on SH-SY5Y cells may increase through up-regulation of histone acetylation through P38MAPK pathway.
出处
《基础医学与临床》
CSCD
北大核心
2011年第9期984-987,共4页
Basic and Clinical Medicine
基金
北京市自然科学基金(7102012)
