GCLC公司
MAPK/ERK通路
GCLM公司
没食子酸
KEAP1型
化学
谷胱甘肽
活性氧
泛素连接酶
生物化学
激酶
抗氧化剂
细胞生物学
泛素
生物
转录因子
酶
基因
作者
Ruibing Feng,Yang Wang,Chengwei He,Yan Yang,Jian‐Bo Wan
标识
DOI:10.1016/j.fct.2017.10.033
摘要
Gallic acid (GA), a natural polyphenol, has been shown to exert a variety of heath promoting effects. We herein investigated the critical role of nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant response in the protection of GA against tert-butyl hydroperoxide (t-BHP)-induced hepatotoxicity in L02 cells. Pretreatment of GA prevented the hepatocytotoxicity induced by t-BHP, as evidenced by the facts that GA suppressed t-BHP-induced cytotoxicity and reactive oxygen species (ROS) generation. GA induced nuclear translocation of Nrf2 along with expression of target proteins, including heme oxygenase-1 (HO-1) and glutamate cysteine ligase catalytic modify subunit (GCLC), and increased intracellular glutathione (GSH) content. Additionally, GA induced phosphorylated activation of extracellular regulated kinase (ERK), and ERK inhibitor PD98059 partially decreased GA-induced hepatoprotection, and downregulated the increased protein expressions of Nrf2, GCLC and HO-1 induced by GA. Interestingly, we found that GA could enhance the thermal stability of Keap1, which indicated the potential interaction between GA and Keap1. Furthermore, molecular docking indicated that GA possibly competed with Nrf2 for binding to Keap1. Collectively, GA effectively protects against t-BHP-induced hepatotoxicity via inducing ERK/Nrf2-mediated antioxidative signaling pathway. Meanwhile, GA disturbs protein-protein interaction between Keap1 and Nrf2 which might also contribute to nuclear translocation of Nrf2.
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