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The complexity of the Nrf2 pathway: beyond the antioxidant response

机译：Nrf2途径的复杂性：超越抗氧化剂反应

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摘要

The NF-E2-related factor 2 (Nrf2)-mediated signalling pathway provides living organisms an efficient and pivotal line of defensive to counteract environmental insults and endogenous stressors. Nrf2 coordinates the basal and inducible expression of antioxidant and Phase II detoxification enzymes to adapt to different stress conditions. The stability and cellular distribution of Nrf2 is tightly controlled by its inhibitory binding protein Kelch-like ECH-associated protein 1. Nrf2 signalling is also regulated by posttranslational, transcriptional, translational and epigenetic mechanisms, as well as by other protein partners, including p62, p21 and IQ motif-containing GTPase activating protein 1. Many studies have demonstrated that Nrf2 is a promising target for preventing carcinogenesis and other chronic diseases, including cardiovascular diseases, neurodegenerative diseases and pulmonary injury. However, constitutive activation of Nrf2 in advanced cancer cells may confer drug resistance. Here, we review the molecular mechanisms of Nrf2 signalling, the diverse classes of Nrf2 activators, including bioactive nutrients and other chemicals, and the cellular functions and disease relevance of Nrf2 and discuss the dual role of Nrf2 in different contexts. (C) 2015 Elsevier Inc. All rights reserved.
机译：NF-E2相关因子2（Nrf2）介导的信号传导途径为活生物体提供了有效而关键的防御线，以抵制环境侵害和内源性应激源。 Nrf2协调抗氧化剂和II期解毒酶的基础表达和诱导表达，以适应不同的胁迫条件。 Nrf2的稳定性和细胞分布受到其抑制性结合蛋白Kelch样ECH相关蛋白1的严格控制。Nrf2信号传导也受翻译后，转录，翻译和表观遗传机制以及包括p62在内的其他蛋白质伴侣的调控， p21和含IQ基序的GTPase活化蛋白1.许多研究表明Nrf2是预防癌变和其他慢性疾病（包括心血管疾病，神经退行性疾病和肺损伤）的有希望的靶标。但是，晚期癌细胞中Nrf2的组成型激活可能会导致耐药性。在这里，我们回顾了Nrf2信号传导的分子机制，Nrf2激活剂的各种类别（包括生物活性营养物质和其他化学物质）以及Nrf2的细胞功能和疾病相关性，并讨论了Nrf2在不同情况下的双重作用。 （C）2015 Elsevier Inc.保留所有权利。

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