The role of Nrf1 and Nrf2 in the regulation of copper-responsive transcription.
The role of Nrf1 and Nrf2 in the regulation of copper-responsive transcription.
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DOI：
10.1016/j.yexcr.2014.01.013
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发表时间：
2014-03-10
影响因子：
3.7
通讯作者：
Freedman JH
中科院分区：
文献类型：
--
作者：
Song MO;Mattie MD;Lee CH;Freedman JH
最近的证据表明，Nrf 2比Nrf 1更有效地激活抗氧化基因。然而，Nrf蛋白在铜响应转录调控中的作用尚未得到很好的解决。我们采用毒理基因组学方法，目前的网络和基因本体论分析结果表明，Nrf 1和Nrf 2是独特的参与铜反应的转录调控HepG 2转录组。无论是Nrf 1或Nrf 2缺陷的细胞更容易受到铜暴露比野生型细胞。用含有ARE或ARE和MRE组合的荧光素酶报告基因转染Nrf 1和Nrf 2缺失细胞，然后用铜处理。在Nrf 2-null（Nrf 2 −/−）细胞中，铜不能激活报告基因的转录，而Nrf 1缺乏不影响铜诱导的激活。Nrf 2的异位表达恢复了Nrf 2 −/−细胞中铜诱导的转录。然而，在Nrf null细胞内MT-1的内在mRNA水平的变化，铜处理后4小时，Nrf 1和Nrf 2同样有助于MT-1的激活，而Nrf 1参与24小时后Nrf 2。这些结果表明，虽然Nrf 2是至关重要的MRE/ARE介导的转录响应铜，Nrf 1可能激活MT-1的表达的机制不同于Nrf 2采用。
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.
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影响因子：
3.8
作者：
Niture SK;Kaspar JW;Shen J;Jaiswal AK
通讯作者：
Jaiswal AK
影响因子：
14.9
作者：
Chorley BN;Campbell MR;Wang X;Karaca M;Sambandan D;Bangura F;Xue P;Pi J;Kleeberger SR;Bell DA
通讯作者：
Bell DA
DOI：
10.1016/s0167-4781(00)00238-4
发表时间：
2000-12-15
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION
影响因子：
--
作者：
Chan, JY;Kwong, M
通讯作者：
Kwong, M
影响因子：
4.8
作者：
FAVREAU, LV;PICKETT, CB
通讯作者：
PICKETT, CB
影响因子：
13.5
作者：
Gong, PF;Cederbaum, AI
通讯作者：
Cederbaum, AI