Roles of Nrf2 in drug and chemical toxicity
Roles of Nrf2 in drug and chemical toxicity
复制标题
DOI：
10.1016/j.cotox.2016.10.004
复制
发表时间：
2016-12-01
影响因子：
4.6
通讯作者：
Copple, Ian M.
中科院分区：
文献类型：
--
作者：
Clarke, Jessica L.;Murray, James B.;Copple, Ian M.
转录因子Nrf2调节许多细胞防御基因的基础和诱导表达，从而保护哺乳动物细胞免受化学和氧化应激的有害影响。在这里，我们简要概述了Nrf2在抵抗药物和化学毒性中的作用，重点介绍了大量体内研究，这些研究表明Nrf2缺失(基因敲除)转基因小鼠对这种侮辱具有高度的敏感性。鉴于Nrf2在癌症耐药中的新作用，我们还考虑了调节Nrf2活性以克服患者化疗耐药的潜在益处和风险。最后，我们强调最近在体外监测Nrf2途径扰动的努力，作为综合风险评估战略的一部分，旨在识别对人类健康有害的化合物。
The transcription factor Nrf2 regulates the basal and inducible expression of numerous cell defence genes, and thus protects mammalian cells against the deleterious effects of chemical and oxidative stress. Here, we provide a concise overview of the role of Nrf2 in protection against drug and chemical toxicity, with a focus on the numerous in vivo studies that have shown heightened sensitivity of Nrf2 null (knockout) transgenic mice to such insults. In light of the emerging role for Nrf2 in driving drug resistance in cancer, we also consider the potential benefits and risks of modulating Nrf2 activity to overcome chemoresistance in patients. Finally, we highlight recent efforts to monitor perturbation of the Nrf2 pathway in vitro as part of integrated risk assessment strategies designed to identify compounds that are hazardous to human health.