Sihvola Virve, Levonen Anna-Liisa
A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio FIN-70211, Finland.
A.I.Virtanen Institute for Molecular Sciences, University of Eastern Finland, Neulaniementie 2, Kuopio FIN-70211, Finland.
Arch Biochem Biophys. 2017 Mar 1;617:94-100. doi: 10.1016/j.abb.2016.10.010. Epub 2016 Oct 18.
Reactive oxygen species (ROS) and products of their reactions with cellular macromolecules such as unsaturated fatty acids have been implicated to be important regulators of signalling processes via oxidation or alkylation of redox active thiol residues in target proteins. One of key redox-sensitive signalling proteins mediating the response to oxidant stress is Keap1 (Kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein 1), which is a negative regulator of transcription factor Nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and the central hub for sensing endogenous and environmental oxidative and electrophilic stress. In this review, we provide an overview of the mechanisms by which Keap1 orchestrates the antioxidant response and how the system can be targeted for therapy.
活性氧（ROS）及其与细胞大分子（如不饱和脂肪酸）反应的产物，被认为是通过氧化或烷基化靶蛋白中氧化还原活性硫醇残基来调节信号传导过程的重要因子。介导对氧化应激反应的关键氧化还原敏感信号蛋白之一是Keap1（具有CNC同源性[ECH]相关蛋白1的类kelch红细胞衍生蛋白），它是转录因子核因子红系2 p45相关因子2（Nrf2）的负调节因子，也是感知内源性和环境性氧化及亲电应激的中心枢纽。在本综述中，我们概述了Keap1协调抗氧化反应的机制以及该系统如何成为治疗靶点。
