NF-kappaB p50 is increased in neurons surviving hippocampal injury.
NF-kappaB p50 is increased in neurons surviving hippocampal injury.
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海马损伤后幸存的神经元中 NF-kappaB p50 增加。
DOI：
10.1006/exnr.2001.7817
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Willing,AE
中科院分区：
文献类型：
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作者：
Pennypacker,KR;Kassed,CA;Eidizadeh,S;Saporta,S;Sanberg,PR;Willing,AE
导致与存活和修复机制相关的基因调节的信号转导通路在损伤存活的神经元中被激活。这些蛋白激酶/磷酸酶级联聚集在转录因子上，转录因子是直接调节基因表达的DNA结合蛋白。本研究检测了脑中动脉闭塞或三甲基锡损伤后7天大鼠海马中NF-κB p50亚基的表达。我们发现，在两种治疗后，整个海马神经元的p50水平都有所增加，不仅局限于细胞体，也局限于过程。在第7天的时间点，氟玉组织化学显示三甲基锡治疗的大鼠海马神经变性，而大脑中动脉闭塞损伤的大鼠未见海马神经变性。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i -κB激酶对抑制剂i -κB蛋白的磷酸化是NF-κB活化的经典步骤，因此我们检测了磷酸化i -κB α免疫反应性作为i -κB激酶活性的指标。损伤后7天，海马各神经元中磷酸化i - κ b α水平升高。免疫印迹法显示，损伤后1天，磷酸化i κ b α水平升高，且升高至少持续7天。这些数据表明，NF-κB信号转导参与了损伤存活神经元的适应性反应。
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.