ERK/CREB信号通路在异菝葜皂苷元促进Aβ损伤SH-SY5Y细胞BDNF表达中的作用  

Role of ERK/CREB signal pathway in promotion of BDNF expression in Aβintoxicated SH-SY5Y cells by smilagenin

作　　者：张瑞[1,2] 夏志明[1] 孙小余 李加梅 张永芳[1,2] 胡雅儿[1,2] 

机构地区：[1]上海交通大学医学院细胞调控研究室,上海200025 [2]上海交通大学医学院转化医学协同创新中心,上海200025

出　　处：《上海交通大学学报（医学版）》2016年第5期642-647,共6页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市卫生局科研计划课题资助项目(20124y007);国家自然科学基金(81573401)~~

摘　　要：目的探讨细胞外信号调节激酶/c AMP反应元件结合蛋白(ERK/CREB)信号通路在异菝葜皂苷元(SMI)促进β-淀粉样肽(Aβ)损伤SH-SY5Y细胞脑源性神经营养因子(BDNF)表达中的作用及其机制。方法建立Aβ损伤SH-SY5Y细胞模型,采用RT-PCR法检测BDNF m RNA的表达,用Western blotting的方法检测p CREB和p ERK的变化,最后通过阻断实验确认ERK/CREB信号通路在SMI促进BDNF m RNA表达中的作用。结果 SMI能促进Aβ损伤SH-SY5Y细胞BDNF m RNA的表达(P=0.000),并能上调信号分子CREB和ERK1/2的磷酸化水平(P=0.001,P=0.000)。用RNA干扰的方法阻断CREB的表达后,SMI促进BDNF m RNA表达的作用完全消失;用U0126阻断ERK1/2磷酸化后,SMI促进p CREB水平升高的作用完全消失。结论 SMI通过ERK/CREB通路促进Aβ损伤SH-SY5Y细胞BDNF m RNA的表达。Objective To investigate the role of extracellular signal regulated kinase / c AM Presponse element binding protein（ ERK / C REB） signaling pathway in prom otion of brain derived neurotrophic factor（ BDNF）expression in β-amyloid（ Aβ） intoxicated SH-SY5 Y cells by smilagenin（ SM I） and relevant m echanism s.Methods The Aβ intoxicated cell model was built and RT-PCR assay was employed to detect the BDNF m RN A expression. Western blotting was used to detect changes in p CREB and p ERK expressions. Finally, the role of ERK / CREB signaling pathway in the prom otion of BDNF m RN A expression by SMI was confirm ed by the use of blocking assay. Results SM I prom oted the BDNF m RN A expression in Aβ intoxicated SH-SY5 Y cells（ P = 0. 000） and up-regulated the phosphorylation level of signal m olecules CREB and ERK1 /2（ P = 0. 001,P = 0. 000）. After blocking the C REB expression by RN A interference, the effect of SM I on promoting the BDNF mRN A expression com pletely vanished. After blocking the ERK1 /2 phosphorylation with U 0126, the effect of SM I on prom oting the increase in p CREB level com pletely vanished. Conclusion SM I prom otes the BDNF mRNA expression in Aβ intoxicated SH-SY5 Y cells through the ERK / CREB pathway.

关 键 词：异菝葜皂苷元 阿尔茨海默症 脑源性神经营养因子 c AMP反应元件结合蛋白 细胞外信号调节激酶1/2 

分 类 号：R749.16[医药卫生—神经病学与精神病学]