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首页> 外文期刊>The European Journal of Neuroscience >Upregulation and activation of the Nrf-1 transcription factor in the lesioned hippocampus.
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Upregulation and activation of the Nrf-1 transcription factor in the lesioned hippocampus.

机译:病变海马中Nrf-1转录因子的上调和激活。

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The Nrf-1 and Nrf-2 transcription factors play a pivotal role in the cellular defence against the toxic effects of reactive oxygen species (ROS). Although ROS are key effectors of neuronal death after ischaemic and traumatic brain injury, it is not known whether Nrf-1 and Nrf-2 are involved in neuroprotective signalling. Here, we analysed the temporal and spatial expression pattern of Nrf-1 and Nrf-2 after unilateral excitotoxic lesion of mouse hippocampus. In marked contrast to previous in vitro studies, where upregulation of these transcription factors on the mRNA level was never detected, we found a strong induction of Nrf-1 mRNA and protein expression in neurons of the lesioned hippocampus, accompanied by a weak elevation of Nrf-2 mRNA levels. Nrf-1 predominantly localized to the nucleus in the injured hippocampus. Furthermore, expression of the cytoprotective enzyme, heme oxygenase-1, a major target of Nrf-1 and Nrf-2 action, was coregulated with Nrf-1 in the same hippocampal neurons, suggesting that Nrf-1 is functionally active. Because Nrf-1 and Nrf-2 are potent inducers of various cytoprotective proteins, our data suggest a role of Nrf-1 and Nrf-2 in neuronal survival after acute brain injury.
机译:Nrf-1和Nrf-2转录因子在细胞防御活性氧(ROS)毒性作用中起着关键作用。尽管ROS是缺血性和外伤性脑损伤后神经元死亡的关键效应器,但尚不清楚Nrf-1和Nrf-2是否参与神经保护信号传导。在这里,我们分析了小鼠海马单侧兴奋性毒性损伤后Nrf-1和Nrf-2的时空表达模式。与以前的体外研究形成鲜明对比的是,从未检测到这些转录因子在mRNA水平上的上调,我们发现受损海马神经元中Nrf-1 mRNA和蛋白表达强烈诱导,同时Nrf升高较弱-2 mRNA水平。 Nrf-1主要位于受损海马的细胞核中。此外,Nrf-1在同一海马神经元中表达了细胞保护酶血红素加氧酶-1(Nrf-1和Nrf-2作用的主要靶标)的表达,表明Nrf-1具有功能活性。由于Nrf-1和Nrf-2是多种细胞保护蛋白的有效诱导剂,因此我们的数据表明Nrf-1和Nrf-2在急性脑损伤后神经元存活中具有重要作用。

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