Nrf2/Keap1-ARE通路的生物学功能及其信号调控
文献类型: 中文期刊
作者: 冯志强;王腾飞;赵善江;郝海生;杜卫华;赵学明;邹惠影;朱化彬;庞云渭
作者机构:
关键词: Nrf2;Keap1;ARE;信号通路;氧化应激
期刊名称:中国畜牧兽医
ISSN: 1671-7236
年卷期: 2022 年 01 期
页码:
收录情况: 北大核心(2020版) ; 科技核心(2021版) ; 农林核心(2020版)
摘要: 氧化应激是机体内一种有害的氧化还原失衡状态,是导致组织损伤和疾病发生的重要因素之一。当前畜牧业生产中出现的畜禽繁殖障碍、抗病力下降、生产性能与畜产品品质降低等都与氧化应激有关。核因子E2相关因子2(nuclear factor erythroid 2related factor,Nrf2)/Kelch样ECH相关蛋白1(Kelch-like ECH-associated protein1,Keap1)-抗氧化应答元件(antioxidant response element,ARE)信号通路是机体对抗氧化应激的最重要防御机制之一,通过调控下游多个细胞保护基因的转录,维持胞内氧化还原平衡及代谢和蛋白质稳态,发挥抗炎、抗癌和抗衰老等生物学功能。Nrf2是一种对氧化应激高度敏感的转录因子,在正常生理状态下,与其负调控蛋白Keap1结合,通过泛素-蛋白酶体系统被泛素化和降解。氧化应激导致Nrf2与Keap1解离,Nrf2转位到细胞核内,与小Maf(sMaf)蛋白形成异二聚体并识别ARE序列,启动下游目标基因的转录。由于Nrf2处于复杂调控网络的中心,其活性受到多个水平的严格调控,包括转录及转录后调控、蛋白质稳定性调控、亚细胞定位调控和翻译后修饰调控等。作者介绍了Nrf2/Keap1-ARE信号通路的分子结构基础、生物学功能、Nrf2活性调控等的研究进展,以期深入了解该通路的调控机制,为提高畜禽健康和提供疾病治疗策略提供理论依据。
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