Over-expression of Nrf2 diminishes ethanol-induced oxidative stress and apoptosis in neural crest cells by inducing an antioxidant response.

Over-expression of Nrf2 diminishes ethanol-induced oxidative stress and apoptosis in neural crest cells by inducing an antioxidant response.
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DOI:
10.1016/j.reprotox.2013.08.003
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发表时间:
2013-12
期刊:
Reproductive toxicology (Elmsford, N.Y.)
影响因子:
--
通讯作者:
Chen SY
Chen SY
中科院分区:
其他
文献类型:
--
作者:
Chen X;Liu J;Chen SY

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核因子红细胞2相关因子(Nrf2)是调节细胞抗氧化防御的关键转录因子。在这项研究中,我们研究了 Nrf2 的过度表达是否可以预防乙醇诱导的神经嵴细胞 (NCC) 氧化应激和细胞凋亡。我们发现,与用对照载体转染的细胞相比,用 pcDNA3.1-Nrf2 转染 NCC 导致对照和乙醇暴露的 NCC 中 Nrf2 蛋白水平显着增加。荧光素酶报告基因检测显示,Nrf2 的过表达显着增加了 NCC 中抗氧化反应元件(ARE)启动子的活性。 Nrf2 过表达还增加了 NCC 中 Nrf2 靶抗氧化剂的蛋白表达和活性。此外,Nrf2 的过度表达显着减少了乙醇暴露的 NCC 中 ROS 的产生并减少了细胞凋亡。这些结果表明,Nrf2 的过度表达可以通过诱导抗氧化反应来防止 NCC 中乙醇诱导的氧化应激和细胞凋亡。
Nuclear factor erythroid 2-related factor (Nrf2) is a key transcription factor that regulates antioxidant defense in cells. In this study, we investigated whether over-expression of Nrf2 can prevent ethanol-induced oxidative stress and apoptosis in neural crest cells (NCCs). We found that transfection of NCCs with pcDNA3.1-Nrf2 resulted in statistically significant increases in the Nrf2 protein levels in control and ethanol-exposed NCCs as compared to the cells transfected with control vector. Luciferase reporter gene assay revealed that over-expression of Nrf2 significantly increased the antioxidant response element (ARE) promoter activity in NCCs. Nrf2 over-expression also increased the protein expression and activities of Nrf2 target antioxidants in NCCs. In addition, over-expression of Nrf2 significantly decreased ROS generation and diminished apoptosis in ethanol-exposed NCCs. These results demonstrate that over-expression of Nrf2 can confer protection against ethanol-induced oxidative stress and apoptosis in NCCs by the induction of an antioxidant response.
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