遗传 ›› 2014, Vol. 36 ›› Issue (6): 519-524.doi: 10.3724/SP.J.1005.2014.0519

• 综述 • 上一篇    下一篇

程序性坏死(Necroptosis)的分子机制

巴微1, 2, 逄越1, 2, 李庆伟1, 2   

  1. 1. 辽宁师范大学生命科学学院, 大连116029;
    2. 辽宁师范大学七鳃鳗研究中心, 大连116029
  • 收稿日期:2013-12-19 修回日期:2014-03-14 出版日期:2014-06-20 发布日期:2014-05-28
  • 通讯作者: 李庆伟,教授,博士生导师,研究方向:细胞生物学。E-mail:liqw@263.net逄越,副教授,硕士生导师,研究方向:细胞生物学。E-mail:pangyue01@163.com E-mail:chifanchoua@163.com
  • 作者简介:巴微,硕士研究生,专业方向:细胞生物学。E-mail:chifanchoua@163.com
  • 基金资助:

    国家重大基础研究发展规划(973计划)项目(编号: 2013CB835304),全国海洋公益项目(编号: 201305016),国家自然科学基金项目(编号: 31170353, 31202020)和大连市科技计划项目(编号:2013E11SF056) 资助

The molecular mechanism of necroptosis

Wei Ba1, 2, Yue Pang1, 2, Qingwei Li1, 2   

  1. 1. College of Life Science, Liaoning Normal University, Dalian 116029, China;
    2. Lamprey Research Center, Liaoning Normal University, Dalian 116029, China
  • Received:2013-12-19 Revised:2014-03-14 Online:2014-06-20 Published:2014-05-28

摘要:

程序性坏死(Necroptosis)是一种不同于凋亡及传统坏死的细胞程序性死亡方式, 可由肿瘤坏死因子受体(Tumor necrosis factor receptor, TNFR)或模式识别受体(Pattern recognition receptor, PRR)调控启动。受体相互作用蛋白(Receptor-interacting protein, RIP)1和3是启动necroptosis的两个关键蛋白, necroptosis启动后需要一系列分子传递和执行死亡信号, 如多核苷酸二磷酸-核糖聚合酶-1(Poly(ADP-ribose) polymerase, PARP-1)、活性氧簇(Reactive oxygen species, ROS)、Ca2+等, 这些分子破坏线粒体及其他细胞器, 最终使细胞在缺乏天冬氨酸半胱氨酸蛋白酶(Caspase)的情况下死亡。Necroptosis细胞可将损伤相关模式分子(Damage-associated molecular patterns, DAMPs)暴露到细胞外, 被吞噬细胞识别并清除。文章对启动necroptosis的受体分子、传递执行细胞坏死的重要分子和坏死细胞的清除过程进行了概述。

关键词: 程序性坏死, 肿瘤坏死因子受体, 受体相互作用蛋白

Abstract:

Programmed necrosis called necroptosis, is different from traditional necrosis and apoptosis, it has attracted considerable attention over the last few years. Necroptosis can be initiated through many factors such as tumor necrosis factor receptor (TNFR) or pattern recognition receptor (PRR), and receptor-interacting protein (RIP) 1 and 3 are two key proteins during the process. A lot of molecules have been characterized as modulators and effectors of necroptosis, including poly(ADP-ribose) polymerase (PARP-1), reactive oxygen species (ROS), Ca2+, which can destruct mitochondria or other organelles and induce cell dead through caspase-independent pathway. Then, damage-associated molecular pattern (DAMP) molecules were released from necroptosis cells, recognized and internalized by phagocytes. Here, we briefly discuss the initiation and execution of necroptosis and the clearance of death cells.

Key words: necroptosis, tumor necrosis factor receptor(TNFR), receptor-interacting protein