摘要
Recent evidences indicated Nrf2 is more potent than Nrf1 in the activation of antioxidant genes. However, the roles of Nrf proteins in the regulation of copper-responsive transcription have not been well addressed. We took the toxicogenomic approach and the present network and Gene Ontology analyses results showed that Nrf1 and Nrf2 are distinctively involved in copper-responsive transcriptional regulation in HepG2 transcriptome. Cells deficient in either Nrf1 or Nrf2 were more susceptible to copper exposure than wild type cells. Nrf1 and Nrf2 null cells were transfected with the luciferase reporters containing either ARE(s) or a combination of ARE(s) and MREs, and then treated with copper. In Nrf2-null (Nrf2−/−) cells, copper did not activate transcription of reporter genes, whereas Nrf1 deficiency did not affect copper-inducible activation. Ectopic expression of Nrf2 restored copper-inducible transcription in Nrf2−/− cells. However, the changes in the intrinsic mRNA levels of MT-1 in Nrf null cells following copper treatment showed that Nrf1 and Nrf2 equally contributed to MT-1 activation after 4 h, while Nrf1involved more than Nrf2 following 24 h exposure. These results suggest that while Nrf2 is crucial for MRE/ARE-mediated transcription in response to copper, Nrf1 may activate MT-1 expression by a mechanism different from that Nrf2 employs.
摘要译文
最近的证据表明Nrf2的是在抗氧化基因的活化比NRF1更有效。然而，NRF蛋白铜响应的转录调控中的作用还没有得到很好的解决。ogenomic方式和现有网络和基因本体分析结果表明，NRF1和Nrf2的是鲜明参与铜应答转录调控HepG2细胞转录组。细胞缺乏任NRF1或Nrf2的更易发生比野生型细胞的铜的曝光。NRF1和Nrf2的空细胞用含有荧光素酶记者或者ARE（S）或为（S）和的MRE的组合，然后用铜处理。在Nrf2的空（Nrf2的SUP/Nrf2的异位表达恢复铜诱导的转录的Nrf2的SUP的变化的MT-1的NRF空细胞下列铜治疗的内在mRNA水平表明，NRF1和Nrf2的同等贡献的MT-1活化后4小时，而Nrf1involved超过Nrf2的以下24个小时暴露。这些结果表明，虽然Nrf2的是至关重要的MRE /响应于铜ARE介导的转录，NRF1可以激活MT-1的表达通过从Nrf2的采用不同的机制。
Min Ok Song[a][1]; Michael D. Mattie[b][1][2]; Chang-Ho Lee[a]; Jonathan H. Freedman[c]. The role of Nrf1 and Nrf2 in the regulation of copper-responsive transcription[J]. Experimental Cell Research, 2014,322(1): 39–50