Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Qilu Hospital, Shandong University, 107 Wen Hua Xi Road, Jinan, Shandong 250012, China.
Pharmacol Rev. 2011 Mar;63(1):218-42. doi: 10.1124/pr.110.002980. Epub 2011 Jan 12.
NADPH oxidase (Nox) has a dedicated function of generating reactive oxygen species (ROS). Accumulating evidence suggests that Nox has an important role in signal transduction in cellular stress responses. We have reviewed the current evidence showing that the Nox system can be activated by a collection of chemical, physical, and biological cellular stresses. In many circumstances, Nox activation fits to the cellular stress response paradigm, in that (1) the response can be initiated by various forms of cellular stresses; (2) Nox-derived ROS may activate mitogen-activated protein kinases (extracellular signal-regulated kinase, p38) and c-Jun NH(2)-terminal kinase, which are the core of the cell stress-response signaling network; and (3) Nox is involved in the development of stress cross-tolerance. Activation of the cell survival pathway by Nox may promote cell adaptation to stresses, whereas Nox may also convey signals toward apoptosis in irreversibly injured cells. At later stage after injury, Nox is involved in tissue repair by modulating cell proliferation, angiogenesis, and fibrosis. We suggest that Nox may have an integral role in cell stress responses and the subsequent tissue repair process. Understanding Nox-mediated redox signaling mechanisms may be of prominent significance at the crossroads of directing cellular responses to stress, aiming at either enhancing the stress resistance (in such situations as preventing ischemia-reperfusion injuries and accelerating wound healing) or sensitizing the stress-induced cytotoxicity for proliferative diseases such as cancer. Therefore, an optimal outcome of interventions on Nox will only be achieved when this is dealt with in a timely and disease-and stage-specific manner.
NADPH 氧化酶（Nox）具有专门的生成活性氧物质（ROS）的功能。越来越多的证据表明，Nox 在细胞应激反应的信号转导中具有重要作用。我们已经回顾了目前的证据，表明 Nox 系统可以被一系列化学、物理和生物细胞应激激活。在许多情况下，Nox 的激活符合细胞应激反应的范式，即（1）反应可以由各种形式的细胞应激启动；（2）Nox 衍生的 ROS 可以激活丝裂原激活的蛋白激酶（细胞外信号调节激酶，p38）和 c-Jun NH2-末端激酶，这是细胞应激反应信号网络的核心；（3）Nox 参与应激交叉耐受的形成。Nox 激活细胞存活途径可能促进细胞适应应激，而 Nox 也可能在不可逆损伤的细胞中传递凋亡信号。在损伤后的后期，Nox 通过调节细胞增殖、血管生成和纤维化参与组织修复。我们认为，Nox 可能在细胞应激反应和随后的组织修复过程中具有整体作用。理解 Nox 介导的氧化还原信号机制可能在指导细胞对应激的反应方面具有重要意义，旨在增强应激抵抗力（如预防缺血再灌注损伤和加速伤口愈合）或使应激诱导的细胞毒性对增殖性疾病（如癌症）敏感。因此，只有在及时和疾病及阶段特异性的方式下处理 Nox，才能实现干预 Nox 的最佳效果。
