神经药理学报 ›› 2011, Vol. 1 ›› Issue (4): 1-5.

• 研究论文 •    下一篇

α-突触核蛋白抑制PC12细胞中BDNF的表达

苑玉和,吴苗苗,胡金凤,陈乃宏   

  1. 天然药物活性物质与功能国家重点实验室中国医学科学院药物研究所北京100050中国
  • 出版日期:2011-08-26 发布日期:2012-11-24
  • 通讯作者: 陈乃宏,男,博士生导师;Tel:+86-010-63165177,Fax:+86-010-63165177,E-mail:Chennh@imm.ac.cn
  • 作者简介:苑玉和,女,博士,副研究员;研究方向:分子神经药理学和神经生物学;Tel:+86-010-63165182,E-mail:yuanyuhe@imm.ac.cn
  • 基金资助:

    国家自然基金项目(No.U832008、30973887、81073078、81102831、90713045、81072541),科技部项目(No.2010DFB32900),国家科技重大专项(No.2012ZX09301002-004)

α-Synuclein Inhibits the Expression of BDNF in PC12 Cells

YUAN Yu-he,WU Miao-miao,HU Jin-feng,CHEN Nai-hong   

  1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Science and Peking Union Medical College,Beijing,100050,China
  • Online:2011-08-26 Published:2012-11-24

摘要: 目的:研究α-突触核蛋白(α-synuclein)对脑源性神经营养因子(brain derived neurophic factor,BDNF)表达的影响。方法:利用分子克隆技术构建α-突触核蛋白真核表达载体并转染哺乳动物细胞,Western Blotting法检测蛋白的表达及蛋白磷酸化的改变;双荧光素酶报告系统检测转录因子的活性。结果:α-突触核蛋白过表达使BDNF表达明显减弱;而报告基因检测方法显示:过表达α-突触核蛋白后,调控BDNF表达的转录因子cAMP反应元件结合蛋白(cAMP response element binding protein,CREB)的转录活性明显受抑制,但并不影响Nurr1的转录活性;Western Blotting 结果显示:过表达α-突触核蛋白后,CREB的133位ser磷酸化显著降低,而Nurr1的表达无显著变化。结论:过表达α-突触核蛋白可能通过抑制转录因子CREB的活性影响BDNF的表达。

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关键词: alpha, -突触核蛋白, 脑源性神经营养因子, 转录因子, 转录活性

Abstract: Objective:To research the effect of α-synuclein on the brain derived neurophic factor (BDNF) expression. Methods:Recombinant plasmids were constructed using molecular techniques and were used to transfect mammalian cells. The protein level was examined by western blotting assay and the activity of transcription factors was tested by dual-luciferase reporter assay system. Results:Overexpression of α-synuclein inhibited the expression of BDNF and attenuated the transcription activity of cAMP response element binding protein (CREB),but did not affect the activity of Nurr1. Besides,CREB ser-133 phosphorylation level was decreased when α-synuclein was overexpressed. Conclusion:Overexpressed α-synuclein down-regulates BDNF probably through depressing the activities of CREB transcription factors.

Key words: alpha, -synuclein, brain derived neurophic factor(BDNF), transcription factor, transactivity

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