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Nrf2参与水生动物氧化应激调控的研究进展
严小军1,2, 祁鹏志1,2, 郭宝英1,2, 李继姬1,2
1.国家海洋设施养殖工程技术研究中心 舟山 316022;2.浙江海洋大学海洋科学与技术学院 舟山 316022
摘要:
环境变化会诱导机体活性氧(reactive oxygen species,ROS)水平升高,从而产生氧化应激。氧化应激对所有生物的生存、生长、发育和进化都具有深远的影响。核因子E2相关因子2(nuclear factor erythroid 2 related factor 2,Nrf2)被公认为细胞氧化应激调控的主导者,与伴侣蛋白Kelch样环氧氯丙烷相关蛋白1(kelch-like ECH-associated protein 1,Keap1)一起控制数百个解毒酶和抗氧化蛋白编码基因的表达。近年来,Nrf2在水生动物中逐渐获得重视,并在一些模式鱼类如斑马鱼、鲤鱼及其他一些鱼类和水生无脊椎动物中得到研究。介绍了Nrf2的结构以及调控机制,回顾了近年来水生动物Nrf2通路参与氧化应激调控所取得的进展。研究表明,Nrf2在水生动物中广泛存在,在非生物(金属、有机污染物、无机盐、药物及微塑料等)、生物(细菌、病毒、有毒藻类)以及生境变化(冰融、盐胁迫)诱导的氧化应激调控中发挥重要作用。Nrf2一经激活入核,在小Maf蛋白的协助下与抗氧化反应元件(antioxidant-response element,ARE)结合,启动一系列ARE驱动基因的表达,并和孕烷X受体(pregnane X receptor,Pxr)、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)以及芳烃受体(aryl hydrocarbon receptor,AhR)等细胞通路协同作用参与一系列生理过程。Nrf2在水生动物响应环境变化过程中发挥重要的细胞保护机制,有望发展成为抗逆育种潜在的基因靶点。
关键词:  核因子E2相关因子2(Nrf2)  氧化应激  水生动物
DOI:10.11693/hyhz20201100316
分类号:
基金项目:国家自然科学基金项目,42020104009号,41976111号,42076119号;舟山市科技计划项目,2020C21119号,2019F12004号。
THE ADVANCES IN RESEARCH OF NRF2 PATHWAY INVOLVED IN OXIDATIVE STRESS REGULATION IN AQUATIC ANIMALS
YAN Xiao-Jun1,2, QI Peng-Zhi1,2, GUO Bao-Ying1,2, LI Ji-Ji1,2
1.National Engineering Research Center of Marine Facilities Aquaculture, Zhoushan 316022, China;2.School of Ocean Science and Technology, Zhejiang Ocean University, Zhoushan 316022, China
Abstract:
Environmental changes can induce the increase of reactive oxygen species (ROS) level, which leads to oxidative stress. Oxidative stress has a profound impact on the survival, growth, development, and evolution of all organisms. The nuclear factor erythroid 2 related factor 2 (Nrf2) has been recognized as a dominant regulator of oxidative stress. Together with Kelch-like ECH associated protein 1 (Keap1), Nrf2 controls the expression of hundreds of detoxification enzymes and antioxidant protein coding genes. In recent years, Nrf2 has been gained with more and more attention in aquatic animal study, and has been studied in some model fish such as zebrafish, carp, other fish, and aquatic invertebrates. In this paper, the structure and regulatory mechanism of Nrf2 is introduced, and the progress of Nrf2 pathway involved in the regulation of oxidative stress in aquatic animals in recent years is reviewed. Studies have shown that Nrf2 exists widely in aquatic animals, and plays an important role in the regulation of oxidative stress induced by abiotic (metals, organic pollutants, inorganic salts, drugs and micro plastics), biological (bacteria, viruses, toxic algae), and habitat changes (ice melting, salt stress). Once Nrf2 is activated into the nucleus, it binds with anti-oxidant response element (ARE) with the help of small Maf protein, and starts the expression of a series of are driven genes, and interacts with pregnane X receptor (Pxr), mitogenactivated protein kinase (MAPK), and aromatic hydrocarbon receptor (AhR) and other cellular pathways are involved in a series of physiological processes. Nrf2 plays an important role in cell protection of aquatic animals in response to environmental changes, and is expected to become a potential gene target for stress resistance breeding.
Key words:  nuclear factor erythroid 2 related factor 2  oxidative stress  aquatic animals
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