基础医学与临床 ›› 2013, Vol. 33 ›› Issue (3): 291-296.

• 研究论文 • 上一篇    下一篇

α-突触核蛋白与Nurr1相互作用增强致小鼠小胶质细胞系肿瘤坏死因子α表达增多

庄颖1,鲁玲玲2,赵春礼2,段春礼3,杨慧4   

  1. 1. 首都医科大学
    2. 首都医科大学北京神经科学研究所
    3. 首都医科大学神经科学研究所
    4. 首都医科大学神经生物学系 北京神经科学研究所
  • 收稿日期:2012-10-22 修回日期:2012-12-28 出版日期:2013-03-05 发布日期:2013-03-05
  • 通讯作者: 杨慧 E-mail:yanghui0105@sina.com
  • 基金资助:
    国家重点基础研究发展计划;胞质NPM突变蛋白调控TRAF6介导的AKT泛素化激活在急性髓系白血病中的作用;北京市教育委员会科技发展计划重点项目;北京市自然科学基金面上项目

Enhancing TNF-α expression is induced by an increased interaction between α-synuclein and Nurr1 in microglial cell line

  • Received:2012-10-22 Revised:2012-12-28 Online:2013-03-05 Published:2013-03-05

摘要: 目的 在BV2细胞中,探讨?-突触核蛋白( ?-Syn)与Nurr1之间是否存在相互作用及其对肿瘤坏死因子?( TNF-?)分泌的影响。方法 用蛋白质免疫共沉淀(Co-IP)和免疫组织化学染色观察?-Syn和Nurr1之间是否存在相互作用,用免疫组织化学和蛋白印迹观察Nurr1核转位,用酶联免疫技术(Elisa)检测TNF-?的释放量。结果 ?-Syn和Nurr1存在共定位,?-Syn和Nurr1可能存在相互作用。 过表达?-Syn时Nurr1的核转位减少,单独过表达?-syn使得TNF-?分泌增加;而同时过表达Nurr1可以明显抑制TNF-?产生。结论 ?-Syn可能通过与Nurr1相互作用从而减少其核转位,导致TNF-?产生增多,这可能是?-Syn介导胶质细胞活化引起炎症的机制之一。

关键词: α-synuclein , Nurr1 , TNF-α , BV2细胞

Abstract: Objective To investigate the interaction between ?-synuclein and Nurr1 and its influence on the production of TNF-?. Methods The association between ?-synuclein and Nurr1 was observed with Co-IP. The co-localization and the nuclear translocation level of Nurr1 was observed by immunocytochemistry. The BV2 cells were transfected with plasmid encoding pCMV-Myc-vector, pCMV-Myc-?-synuclein with/without Nurr1-pAAV for 24 hours, Media were collected and used Elisa to quantify the level of TNF-?. Result Immunocytochemistry images have shown that ?-synuclein was co-locolization with Nurrl, meanwhile, Co-IP results further showed that ?-synuclein may interacted with Nurr1. Nurr1 nuclear translocation level decreased and TNF-? production increased significantly in ?-synucein overexpression BV2 cells. However, Nurr1 could attenuate the increase of TNF-? induced by ?-synucein in double-transfected BV2 cells. Conclusion ?-Syn associated with Nurr1 and this association contributed to Nurr1 inactivation and its downstream gene TNF-?. The results may suggest that one of mechanisms of inflammation with glia activation induced by ?-synuclein, which might provide critical insights into the pathogenesis of PD and other neurodegenerative diseases.

Key words: α-synuclein , Nurr1, TNF-α, BV2 cells

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