药学学报, 2018, 53(12): 1995-2005
引用本文:
李晓华, 唐乃夫, 厉永强, 刘彬. p62/Nrf2信号途径在细胞保护中的作用[J]. 药学学报, 2018, 53(12): 1995-2005.
LI Xiao-hua, TANG Nai-fu, LI Yong-qiang, LIU Bin. Cytoprotective effect of p62/Nrf2 signaling pathway[J]. Acta Pharmaceutica Sinica, 2018, 53(12): 1995-2005.

p62/Nrf2信号途径在细胞保护中的作用
李晓华1, 唐乃夫1, 厉永强2, 刘彬1
1. 河南大学护理与健康研究所, 河南 开封 475004;
2. 河南大学基础医学院, 河南 开封 475004
摘要:
机体内外各种因素导致的氧化应激,破坏细胞内氧化还原平衡,激活或抑制许多信号通路和一些信号介导分子。Keap1-Nrf2-ARE信号通路是机体维持氧化还原平衡和消除有毒有害物质损伤作用的重要通道之一,通过诱导具有细胞保护功能的基因表达,应对氧化应激和有害化学物质的破坏作用。一般认为,维持Nrf2信号通路及其细胞保护作用是预防肿瘤发生的一种方式,但如果控制Nrf2降解的基因突变使Nrf2持续活化也可能促进肿瘤发生,或促进肿瘤细胞对化疗药物产生抵抗作用。自噬过程也与复杂的细胞功能相关,通过降解和去除细胞内有害的蛋白质和受损的细胞器,维持细胞的正常功能。已有研究显示,Keap1-Nrf2-ARE信号通路与自噬通路的相互联系和相互影响是由自噬适配子蛋白p62与Keap1的直接作用完成的。自噬作用失调则以p62依赖的方式增强Nrf2的活性,与多种疾病特别是恶性肿瘤的发病及治疗有关。本文就p62介导的Nrf2通路激活的调控机制及其与神经系统疾病、心血管疾病和恶性肿瘤的关系进行综述。
关键词:    p62      氧化应激      核因子E2相关因子2      Keap1      自噬      细胞保护作用     
Cytoprotective effect of p62/Nrf2 signaling pathway
LI Xiao-hua1, TANG Nai-fu1, LI Yong-qiang2, LIU Bin1
1. Institute of Nursing and Health, Henan University, Kaifeng 475004, China;
2. School of Basic Medical Science, Henan University, Kaifeng 475004, China
Abstract:
The Nrf2-Keap1-ARE pathway is an important signaling axis that functions to protect cells against oxidative stress and harmful chemicals through the induction of cytoprotective genes. The maintenance and protective role of Nrf2 pathway has been recognized as a means for chemoprevention. On the other hand, constitutive activation of Nrf2, due to somatic mutations of genes that control Nrf2 degradation, promotes carcinogenesis and imparts chemoresistance to cancer cells. Autophagy is another tightly regulated complex cellular process that functions as a cellular quality control system to remove damaged proteins or organelles. Recently, these two cellular pathways were shown to intersect through the direct interaction between p62 (an autophagy adaptor protein) and Keap1. Dysregulation of autophagy was shown to result in prolonged activation of Nrf2 in a p62-dependent manner, which is associated with the pathogenesis and therapies of several human diseases including cancer. In this review, we discuss the molecular mechanisms of p62-mediated Nrf2 signaling pathway, with a special emphasis on their impact on nervous system disease, cardiovascular disease and cancer.
Key words:    p62    oxidative stress    nuclear factor erythroid 2-related factor 2    Keap1    autophagy    cytoprotection   
收稿日期: 2018-08-03
DOI: 10.16438/j.0513-4870.2018-0149
基金项目: 国家自然科学基金资助项目(20872028,21072045).
通讯作者: 厉永强,Tel:86-371-23885557,E-mail:liyongqiang@vip.henu.edu.cn;刘彬,Tel:86-371-23880399,E-mail:lbgood5912@sina.com
Email: liyongqiang@vip.henu.edu.cn;lbgood5912@sina.com
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