NF-κB p50 Is Increased in Neurons Surviving Hippocampal Injury
NF-κB p50 Is Increased in Neurons Surviving Hippocampal Injury
复制标题
海马损伤后幸存的神经元中 NF-κB p50 增加
作者：
K. Pennypacker;C. Kassed;S. Eidizadeh;S. Saporta;P. Sanberg;A. Willing
损伤后存活的神经元中激活了导致与存活和修复机制相关的基因调节的信号转导途径。这些蛋白激酶/磷酸酶级联聚合在转录因子上，转录因子是直接调节基因表达的DNA结合蛋白。在这项研究中，我们检测了NF-κB B p50亚单位在大鼠大脑中动脉闭塞或三甲基锡治疗造成的损伤后7天海马中的表达。我们发现两种治疗后整个海马神经元中的p50水平增加，不仅局限于细胞体，而且还存在于过程中。在第7天的时间点，Fluoro-Jade组织化学显示三甲基锡处理的大鼠海马神经变性，但在大脑中动脉闭塞的损伤中没有。p50在Fluoro-Jade阳性变性细胞中不表达，支持该转录亚基在神经存活中的作用。由于抑制剂IκB蛋白被IκB激酶磷酸化是NF-κB活化的经典步骤，因此将磷酸化I κBα免疫反应性作为IκB激酶活性的指标进行检查。伤后7天，海马神经元磷酸化I κBα水平升高。磷酸化I κBα的免疫印迹显示损伤后1天水平升高，并保持升高至少7天。这些数据表明NF-κB信号转导参与了损伤后存活神经元的适应性反应。
Abstract Signal transduction pathways that lead to the modulation of genes related to survival and repair mechanisms are activated in neurons that survive injury. These protein kinase/phosphatase cascades converge on transcription factors, the DNA binding proteins that directly regulate gene expression. In this study we examined expression of the NF-κB p50 subunit in the rat hippocampus 7 days after injury caused by middle cerebral artery occlusion or trimethyltin treatment. We found increased levels of p50 in neurons throughout the hippocampus after both treatments, localized not only in cell bodies but also in processes. At the 7-day time point, Fluoro-Jade histochemistry revealed hippocampal neurodegeneration in trimethyltin-treated rats but not in those lesioned by middle cerebral artery occlusion. p50 was not expressed in Fluoro-Jade-positive degenerating cells, supporting the role of this transcriptional subunit in neurosurvival. Because phosphorylation of the inhibitor IκB protein by IκB kinase is the classic step in NF-κB activation, phospho-IκBα immunoreactivity was examined as an indication of IκB kinase activity. Levels of phospho-IκBα were increased in neurons throughout the hippocampus 7 days postinjury. Immunoblotting for phospho-IκBα demonstrated increased levels 1 day postinjury that remained elevated for at least 7 days. These data suggest that NF-κB signal transduction is involved in an adaptive response of neurons that survive injury.
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DOI：
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10.1016/0169-328x(95)00229-l
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MOLECULAR BRAIN RESEARCH
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