二苯乙烯苷对神经细胞淀粉样肽前体蛋白表达的影响及其与CREB调节相关的作用机制

doi:10.3969/j.issn.1006-7795.2017.06.012

首都医科大学学报 ›› 2017, Vol. 38 ›› Issue (6): 835-840.doi: 10.3969/j.issn.1006-7795.2017.06.012

• 神经系统疾病的基础和临床研究 • 上一篇下一篇

二苯乙烯苷对神经细胞淀粉样肽前体蛋白表达的影响及其与CREB调节相关的作用机制

尹晓敏^1,2, 徐婷², 戴伍飞², 钱嘉逸², 陈晨¹, 张兰¹, 李林¹

1. 首都医科大学宣武医院药物研究室北京市神经药物工程技术研究中心, 北京 100053;
2. 南通大学医学院生物化学与分子生物学系, 江苏南通 226001

收稿日期:2017-10-01 出版日期:2017-11-21 发布日期:2017-12-16
通讯作者: 李林 E-mail:linlixw@126.com
基金资助:
国家自然科学基金（81273498，81473373，81503077），国家重大新药创制重大专项（2015ZX09101016001），江苏省大学生创新训练计划项目（201610304095x）。

Effects of tetrahydroxystilbene glucoside on amyloid precursor protein expression in nerve cells and its mechanism related to CREB regulation

Yin Xiaomin^1,2, Xu Ting², Dai Wufei², Qian Jiayi², Chen Chen¹, Zhang Lan¹, Li Lin¹

1. Department of Pharmacology, Xuanwu Hospital, Capital Medical University, Beijing Engineering Research Center for Nerve System Drugs, Beijing 100053, China;
2. Department of Biochemistry, Medical School of Nantong University, Nantong 226001, Jiangsu Province, China

Received:2017-10-01 Online:2017-11-21 Published:2017-12-16
Supported by:
This study was supported by National Natural Science Foundation of China (81273498, 81473373, 81503077), National Science and Technology Major Project for New Drug Research and Development of China (2015ZX09101-016), Jiangsu Students' Innovation and Entrepreneurship Training Program (201610304095x).

摘要/Abstract

摘要： 目的探讨二苯乙烯苷（tetrahydroxystilbene glucoside，TSG）对培养神经细胞淀粉样肽前体蛋白（amyloid precursor protein，APP）表达的影响及其作用机制。方法应用Western blotting法检测APP和cAMP效应元件结合蛋白（cAMP responsive element-binding protein，CREB）的表达。用Matinspector软件分析APP启动子区CRE顺式反应元件；构建不同长度APP启动子区荧光素酶表达质粒；用双荧光素酶报告基因系统检测细胞中荧光素酶活性。结果由Forskolin激活SH-SY5Y细胞中CREB的同时可下调APP表达，成功构建了含有CRE元件的APP启动子区荧光素酶表达质粒。TSG能够抑制SH-SY5Y细胞内APP表达，并对APP启动子转染细胞内含有CRE1和2的APP荧光素酶报告基因质粒表达有显著抑制作用。结论 TSG能够下调神经细胞中APP的表达，其机制可能与影响CREB与CRE元件的结合有关。

关键词: 二苯乙烯苷, 淀粉样肽前体蛋白, cAMP效应元件结合蛋白, 阿尔茨海默病

Abstract: Objective To explore the effects of tetrahydroxystilbene glucoside (TSG) on the expression of amyloid precursor protein (APP) and its mechanism in cultured nerve cells.Methods The expression of APP and cAMP responsive element-binding protein (CREB) was detected by Western blotting assay. The CRE cis-elements of APP promoter were analyzed by Matinspector software. The plasmids expressing serial deletion mutants of APP promoter were constructed. The luciferase activity in cells was measured by luciferase double reporter gene system. Results Activation of CREB by Forskolin down-regulated APP expression in SH-SY5Y cells. The luciferase expression plasmids of APP promoter containing CRE elements were successfully constructed. TSG treatment decreased APP level in SH-SY5Y cells, and reduced luciferase activity of APP reporter gene containing CRE1 and CRE2 cis-elements in APP promoter plasmids-transfected cells.Conclusion TSG down-regulated APP expression in nerve cells, and its mechanism may be related to affecting the binding of CREB with CRE cis-elements.

Key words: tetrahydroxystilbene glucoside, amyloid precursor protein, cAMP responsive element-binding protein, Alzheimer's disease

中图分类号:

R749.1

尹晓敏, 徐婷, 戴伍飞, 钱嘉逸, 陈晨, 张兰, 李林. 二苯乙烯苷对神经细胞淀粉样肽前体蛋白表达的影响及其与CREB调节相关的作用机制[J]. 首都医科大学学报, 2017, 38(6): 835-840.

Yin Xiaomin, Xu Ting, Dai Wufei, Qian Jiayi, Chen Chen, Zhang Lan, Li Lin. Effects of tetrahydroxystilbene glucoside on amyloid precursor protein expression in nerve cells and its mechanism related to CREB regulation[J]. Journal of Capital Medical University, 2017, 38(6): 835-840.

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二苯乙烯苷对神经细胞淀粉样肽前体蛋白表达的影响及其与CREB调节相关的作用机制

Effects of tetrahydroxystilbene glucoside on amyloid precursor protein expression in nerve cells and its mechanism related to CREB regulation

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