Fuse Yuji, Kobayashi Makoto
Department of Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
Molecules. 2017 Mar 9;22(3):436. doi: 10.3390/molecules22030436.
The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Its regulatory mechanisms, e.g., stress-sensing mechanism, proteasome-based regulation of Nrf2 activity and selection of target genes, have been elucidated mainly in mammals. In addition, emerging model animals, such as zebrafish, fruit fly and , have been shown to have similar anti-stress systems to mammals, suggesting that analogous defense systems are widely conserved throughout the animal kingdom. Experimental evidence in lower animals provides important information beyond mere laboratory-confined utility, such as regarding how these systems transformed during evolution, which may help characterize the mammalian system in greater detail. Recent advances in genome projects of both model and non-model animals have provided a great deal of useful information toward this end. We herein review the research on Keap1-Nrf2 and its analogous systems in both mammals and lower model animals. In addition, by comparing the amino acid sequences of Nrf2 and Keap1 proteins from various species, we can deduce the evolutionary history of the anti-stress system. This combinatorial approach using both experimental and genetic data will suggest perspectives of approach for researchers studying the stress response.
Keap1-Nrf2系统是一种针对氧化应激和外源性应激的进化保守防御机制。其调控机制，如应激感应机制、基于蛋白酶体对Nrf2活性的调控以及靶基因的选择，主要在哺乳动物中得到阐明。此外，新兴的模式动物，如斑马鱼、果蝇等，已被证明具有与哺乳动物相似的抗应激系统，这表明类似的防御系统在整个动物界广泛存在。低等动物的实验证据提供了超出单纯实验室应用的重要信息，例如这些系统在进化过程中是如何转变的，这可能有助于更详细地描述哺乳动物系统。模式动物和非模式动物基因组计划的最新进展为此提供了大量有用信息。我们在此综述了哺乳动物和低等模式动物中Keap1-Nrf2及其类似系统的研究。此外，通过比较不同物种Nrf2和Keap1蛋白的氨基酸序列，我们可以推断抗应激系统的进化历史。这种结合实验和遗传数据的方法将为研究应激反应的研究人员提供研究方法的视角。
