Trachootham Dunyaporn, Lu Weiqin, Ogasawara Marcia A, Nilsa Rivera-Del Valle, Huang Peng
Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
Antioxid Redox Signal. 2008 Aug;10(8):1343-74. doi: 10.1089/ars.2007.1957.
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) play important roles in regulation of cell survival. In general, moderate levels of ROS/RNS may function as signals to promote cell proliferation and survival, whereas severe increase of ROS/RNS can induce cell death. Under physiologic conditions, the balance between generation and elimination of ROS/RNS maintains the proper function of redox-sensitive signaling proteins. Normally, the redox homeostasis ensures that the cells respond properly to endogenous and exogenous stimuli. However, when the redox homeostasis is disturbed, oxidative stress may lead to aberrant cell death and contribute to disease development. This review focuses on the roles of key transcription factors, signal-transduction pathways, and cell-death regulators in affecting cell survival, and how the redox systems regulate the functions of these molecules. The current understanding of how disturbance in redox homeostasis may affect cell death and contribute to the development of diseases such as cancer and degenerative disorders is reviewed. We also discuss how the basic knowledge on redox regulation of cell survival can be used to develop strategies for the treatment or prevention of those diseases.
活性氧(ROS)和活性氮(RNS)在细胞存活的调节中发挥着重要作用。一般来说,适度水平的ROS/RNS可能作为促进细胞增殖和存活的信号,而ROS/RNS的严重增加则可诱导细胞死亡。在生理条件下,ROS/RNS生成与消除之间的平衡维持着氧化还原敏感信号蛋白的正常功能。正常情况下,氧化还原稳态确保细胞对内源和外源刺激做出适当反应。然而,当氧化还原稳态受到干扰时,氧化应激可能导致异常细胞死亡并促进疾病发展。本综述重点关注关键转录因子、信号转导通路和细胞死亡调节因子在影响细胞存活中的作用,以及氧化还原系统如何调节这些分子的功能。综述了目前对氧化还原稳态紊乱如何影响细胞死亡并导致癌症和退行性疾病等疾病发展的理解。我们还讨论了关于细胞存活氧化还原调节的基础知识如何用于制定治疗或预防这些疾病的策略。