Competition of nuclear factor-erythroid 2 factors related transcription factor isoforms, Nrf1 and Nrf2, in antioxidant enzyme induction.
Competition of nuclear factor-erythroid 2 factors related transcription factor isoforms, Nrf1 and Nrf2, in antioxidant enzyme induction.
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DOI：
10.1016/j.redox.2013.01.005
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发表时间：
2013
期刊：
影响因子：
11.4
通讯作者：
Forman, Henry Jay
中科院分区：
文献类型：
--
作者：
Chepelev, Nikolai L.;Zhang, Hongqiao;Liu, Honglei;McBride, Skye;Seal, Andrew J.;Morgan, Todd E.;Finch, Caleb E.;Willmore, William G.;Davies, Kelvin J. A.;Forman, Henry Jay
尽管Nrf2（核因子-红细胞2 p45亚基相关因子2）通过亲电反应元件（EpRE）调控多种抗氧化和细胞保护基因的表达已被证实，但Nrf2/EpRE与Nrf1（一个密切相关的转录因子）的相互作用尚不清楚。由于蛋白质水解或替代翻译，Nrf1已被发现为不同大小的蛋白质，p120， p95和p65，它们被描述为EpRE的激活剂或Nrf2的竞争性抑制剂。我们以谷氨酸半胱氨酸连接酶的催化亚基和修饰亚基（GCLC和GCLM）为模型，研究了Nrf1对e预调节基因表达的影响，并探讨了Nrf1在衰老和慢性暴露于空气中纳米颗粒物质（nPM）时改变其表达的潜在作用。Nrf1敲除导致人支气管上皮细胞（HBE1）中GCLC和GCLM的表达增加。Nrf2与p120或p65联合过表达降低或无法进一步提高GCLC-和GLCM-EpRE荧光素酶活性。所有已知形式的Nrf1蛋白，在随年龄增长或对nPM反应的小鼠肺中保持不变。我们的研究表明Nrf1在体外可以抑制EpRE的活性，而Nrf1在体内的确切作用还需要进一步的研究。我们得出结论，Nrf1可能不是直接导致在老年动物中观察到的nrf2依赖性抗氧化和细胞保护基因诱导能力丧失的原因。Nrf1敲除增加人支气管上皮细胞中GCLC和GCLM的表达。过表达Nrf1形式p120或p65增加GCLC-和GLCM-EpRE荧光素酶活性。过度表达的Nrf2与Nrf1形式相互竞争。随着年龄的增长，Nrf1在小鼠肺中的表达形式不会改变。Nrf1在暴露于纳米颗粒空气污染中不会改变。
Although the Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2) regulated expression of multiple antioxidant and cytoprotective genes through the electrophile responsive element (EpRE) is well established, interaction of Nrf2/EpRE with Nrf1, a closely-related transcription factor, is less well understood. Due to either proteolysis or alternative translation, Nrf1 has been found as proteins of varying size, p120, p95, and p65, which have been described as either activators of EpRE or competitive inhibitors of Nrf2. We investigated the effect of Nrf1 on EpRE-regulated gene expression using the catalytic and modifier subunits of glutamate cysteine ligase (GCLC and GCLM) as models and explored the potential role of Nrf1 in altering their expression in aging and upon chronic exposure to airborne nano-sized particulate matter (nPM). Nrf1 knockout resulted in the increased expression of GCLC and GCLM in human bronchial epithelial (HBE1) cells. Overexpression Nrf2 in combination with either p120 or p65 diminished or failed to further increase the GCLC- and GLCM-EpRE luciferase activity. All known forms of Nrf1 protein, remained unchanged in the lungs of mice with age or in response to nPM. Our study shows that Nrf1 could inhibit EpRE activity in vitro, whereas the precise role of Nrf1 in vivo requires further investigations. We conclude that Nrf1 may not be directly responsible for the loss of Nrf2-dependent inducibility of antioxidant and cytoprotective genes observed in aged animals. ► Nrf1 knockout increased GCLC and GCLM expression in human bronchial epithelial cells. ► Overexpressed Nrf1 forms p120 or p65 increased GCLC- and GLCM-EpRE luciferase activity. ► Overexpressed Nrf2 competes with Nrf1 forms. ► Nrf1 forms are unchanged in the lungs of mice by age. ► Nrf1 forms are unchanged in exposure to nanoparticulate air pollution.
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影响因子：
7.4
作者：
Zhang, Hongqiao;Liu, Honglei;Davies, Kelvin J. A.;Sioutas, Constantinos;Finch, Caleb E.;Morgan, Todd E.;Forman, Henry Jay
通讯作者：
Forman, Henry Jay
影响因子：
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NRF2：氧化应激中的INRF2（KEAP1）信号传导。
影响因子：
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作者：
Kaspar, James W.;Niture, Suryakant K.;Jaiswal, Anil K.
通讯作者：
Jaiswal, Anil K.
影响因子：
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