氧化和化学应激的防御性转导通路——Nrf2/ARE

Nrf2/ARE是近年新发现的机体抵抗内外界氧化和化学等刺激的防御性转导通路．生理条件下，NF-E2相关因子2(Nrf2，NF-E2-related factor 2)在细胞质中与Keap1结合处于非活性、易降解的状态.在内外界自由基和化学物质刺激时，Keap1的构象改变或者Nrf2直接被磷酸化，导致Nrf2与Keap1解离而活化．活化的Nrf2进入细胞核，与抗氧化反应元件(ARE)结合，启动ARE下游的Ⅱ相解毒酶、抗氧化蛋白、蛋白酶体/分子伴侣等基因转录和表达以抵抗内外界的有害刺激．MAPK、PI3K/AKT、PKC等信号通路分子广泛参与了Nrf2的活化和核转位过程，但是具体何种通路被激动、何种通路发挥主导作用，取决于刺激物种类、刺激方式和细胞类型．本文就Nrf2分子结构、Nrf2活化机制、Nrf2/ARE调控的下游基因、与Nrf2相关的信号通路分子以及其在肿瘤、炎症、衰老等应用领域的最新进展进行综述．

Defensive Pathway of Nrf2/ARE Involved in Oxidative and Chemical Stress

Nrf2(NF-E2-related factor 2)/ARE(antioxidant response element)is a novel defensive pathway involved in oxidative and chemical stress of cells.Under physiological conditions,Nrf2 binds to kelch-like ECH-associated protein-1(Keap1)in the cytoplasm,remains inactivated and easy to be degradated.Under oxidative or chemical stress,Keap1 modification or Nrf2 phosphorylation result in activation of Nrf2 through its dissociation from Keap1.The activated Nrf2 translocates into the nucleus and interacts with ARE.The e...