Nuclear factor kappa B-mediated kainate neurotoxicity in the rat and hamster hippocampus

Administration of the excitotoxin kainate produces seizure activity and selective neuronal death in various brain areas. We examined the degeneration pattern of hippocampal neurons following systemic injections of kainate in the hamster and the rat. As reported, treatment with kainate resulted in severe neuronal loss in the hilus and CA3 in the rat. While the hilar neurons were also highly vulnerable to kainate in the hamster, neurons in the CA1 area, but not CA3, were highly sensitive to kainate. In both animals, immunoreactivity to anti-p50 nuclear factor kappa B antibody was increased in nuclei of the hilar neurons within 4 h following administration of kainate. Kainate treatment also increased the nuclear factor kappa B immunoreactivity in hamster CA1 neurons and rat CA3 neurons 24 h later. Neurons showing intense nuclear factor kappa B signal were stained with acid fuchsin. Kainate also increased DNA binding activity of p50 and p65 nuclear factor kappa B in the nuclear extract of the hippocampal formation as analysed by electrophoretic mobility shift assay in the hamster, suggesting that activation of nuclear factor kappa B may contribute to kainate-induced hippocampal degeneration. Administration of 100 nmol dizocilpine maleate 3 h prior to kainate attenuated kainate-induced activation of nuclear factor kappa B and neuronal death in CA1 in the hamster. The present study provides evidence that the differential vulnerability of neurons in the rat and the hamster hippocampus to kainate is partly mediated by mechanisms involving N-methyl-D-aspartate-dependent activation of nuclear factor kappa B.     

超抗原和核转录因子

在超抗原对真核生物免疫识别的过程中,核转录因子在细胞因子基因调控方面起着重要作用.当不同的细胞在受到不同的超抗原刺激时,众多核转录因子的激活途径和调控细胞因子的表达也具有多样性.     

转录因子的氧化还原调节

细胞内氧化和抗氧化物质的平衡影响着细胞的生长、分化、凋亡和坏死等。活性氧(reactive oxygenspecies ROS)是一类性质十分活泼的化学基团,它主要包括超氧自由基、羟自由基、氢过氧化物自由基、过氧化氢和单线态氧。以往人们对ROS的研究主要集中在它的病理作用上。近年来,随着分子生物学技术的发展和应用,ROS的生理作用越来越引起人们的关注。目前,细胞内氧化物、抗氧化物以及氧化还原态的其它决定因素对细胞内转录因子活化和继之发生的基因表达的调节已成为研究的热点。大量转录因子的活性及其与DNA的结合活性,是受细胞内的氧化还原…