细胞内的氧化还原感受器蛋白与氧化还原信号转导  

Intracellular redox-sensing proteins and redox signal transduction

作　　者：魏亚萍 王媛 郭晓笋 蒋凡 WEI Yaping;WANG Yuan;GUO Xiaosun;JIANG Fan(Department of Physiology and Pathophysiology, School of Basic Medicine,Jinan 250012, China;Department of Emergency,Qilu Hospital,Jinan 250012, China;The Key Laboratory of Cardiovascular Remodeling and Function Research,Chinese Ministry of Education and Chinese Ministry of Health, Shandong University,Jinan 250012, China)

机构地区：[1]山东大学基础医学院生理与病理生理学系,山东济南250012 [2]山东大学齐鲁医院急诊科,山东济南250012 [3]教育部和国家卫计委心血管重构和功能研究重点实验室,山东济南250012

出　　处：《中国病理生理杂志》2018年第1期183-187,共5页Chinese Journal of Pathophysiology

基　　金：助项目(No.31471087;No.81201391;No.81401571);山东省自然科学基金资助项目(No.ZR2014HM014)

摘　　要：氧化还原反应是哺乳动物细胞存活所必需的，在细胞内的生化反应及代谢过程中氧化与还原占据着重要的位置。细胞内环境中氧化还原状态的轻微改变可能对细胞的生物活性产生重大影响。理论上，细胞内氧化还原状态的改变必须通过测定不同氧化还原电子对的还原电位来定量［1-2］。但在实际的生物学研究当中，人们所说的氧化还原状态通常是指胞内或细胞周边活性氧簇（reactiveoxygenspecies，ROS）水平的相对高低。活性氧的大量产生可能对细胞造成氧化损伤，即我们通常所说的“氧化应激（oxidativestress）”状态。目前大量研究显示，氧化应激与心血管系统疾病、神经退行性疾病、糖脂代谢疾病，以及衰老的过程密切相关。但是值得我们关注的是，在研究疾病发生机制的过程中，我们不应该简单地把ROS产生增加等同于氧化应激损伤。实际上，细胞内存在多种对氧化还原状态敏感的蛋白，氧化还原状态的改变可以影响这些蛋白的功能，并对其下游的信号通路产生调控作用。因此我们可以认为这些蛋白分子是细胞内氧化还原状态的感受器（redoxsensor）。这些氧化还原感受器能够被ROS激活，而且在很多情况下这些氧化还原敏感的信号蛋白能够介导细胞的保护作用，提高细胞的应激耐受水平。因此，深入挖掘ROS产生背后是否还隐藏有更复杂、更具特异性的信号转导通路，可能为发现疾病发生发展过程中新的调控机制提供线索。Many signaling proteins in mammalian cells are sensitive to the changes of redox environment,which may specifically affect functions of these proteins,thereby modulating their downstream effects.These signaling proteins are thought to be intracellular redox sensors.Redox-sensing functions have been observed in a variety of transcription factors,kinases,phosphatases,ion channels,and cytoskeletal/structural proteins,while the list is still expanding.We propose that many proteins with redox-sensing functions remain to be identified,and our understanding on the complexity of the redox signaling network in cells is incomplete.In this article,we provide an overview of some established mammalian intracellular redox sensors.It is suggested that,when we study pathophysiological mechanisms of disease,we should keep it in mind that oxidative damage to macromolecules is not the only consequence of increased reactive oxygen production.Rather,changes in redox balance may be linked to multiple specific pathways that are capable of transducing redox signals and regulating various fundamental cellular functions.Aberrant activation or inactivation of these redox signaling mechanisms may have significant contributions to the pathogenesis of diseases.

关 键 词：氧化还原 信号转导 活性氧簇 

分 类 号：R363[医药卫生—病理学] R329.2[医药卫生—基础医学]