Department of Experimental and Clinical Biomedical Sciences "Mario Serio", University of Florence, 50134 Florence, Italy.
Cells. 2023 Apr 13;12(8):1154. doi: 10.3390/cells12081154.
Oxidative stress regulates many physiological and pathological processes. Indeed, a low increase in the basal level of reactive oxygen species (ROS) is essential for various cellular functions, including signal transduction, gene expression, cell survival or death, as well as antioxidant capacity. However, if the amount of generated ROS overcomes the antioxidant capacity, excessive ROS results in cellular dysfunctions as a consequence of damage to cellular components, including DNA, lipids and proteins, and may eventually lead to cell death or carcinogenesis. Both in vitro and in vivo investigations have shown that activation of the mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) pathway is frequently involved in oxidative stress-elicited effects. In particular, accumulating evidence identified a prominent role of this pathway in the anti-oxidative response. In this respect, activation of krüppel-like factor 2/4 and nuclear factor erythroid 2-related factor 2 emerged among the most frequent events in ERK5-mediated response to oxidative stress. This review summarizes what is known about the role of the MEK5/ERK5 pathway in the response to oxidative stress in pathophysiological contexts within the cardiovascular, respiratory, lymphohematopoietic, urinary and central nervous systems. The possible beneficial or detrimental effects exerted by the MEK5/ERK5 pathway in the above systems are also discussed.
氧化应激调节许多生理和病理过程。事实上，基础水平的活性氧（ROS）的适度增加对于各种细胞功能是必不可少的，包括信号转导、基因表达、细胞存活或死亡以及抗氧化能力。然而，如果产生的 ROS 量超过抗氧化能力，过多的 ROS 会导致细胞功能障碍，从而导致细胞成分（包括 DNA、脂质和蛋白质）受损，并最终可能导致细胞死亡或癌变。体外和体内研究均表明，丝裂原活化蛋白激酶激酶 5/细胞外信号调节激酶 5（MEK5/ERK5）途径的激活常涉及氧化应激引起的效应。特别是，越来越多的证据表明该途径在抗氧化反应中起着重要作用。在这方面，在 ERK5 介导的氧化应激反应中，激活 Krüppel 样因子 2/4 和核因子红细胞 2 相关因子 2 是最常见的事件之一。这篇综述总结了 MEK5/ERK5 途径在心血管、呼吸、淋巴血液、泌尿和中枢神经系统的病理生理环境中对氧化应激反应的作用。还讨论了 MEK5/ERK5 途径在上述系统中产生的可能有益或有害的影响。
