Neurotrophic factors increase tumor necrosis factor-α-induced nuclear translocation of NF-κB in rat PC12 cells
Neurotrophic factors increase tumor necrosis factor-α-induced nuclear translocation of NF-κB in rat PC12 cells
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DOI：
10.1016/j.neulet.2005.09.031
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发表时间：
2006-01-16
影响因子：
2.5
通讯作者：
Nakanishi, M
中科院分区：
文献类型：
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作者：
Furuno, T;Nakanishi, M
神经营养因子通过与酪氨酸激酶受体Trks和肿瘤坏死因子（TNF）受体样分子p75神经营养因子受体结合来调节神经元的存活和分化并控制神经突的生长。促炎细胞因子TNF也影响神经元细胞的存活和凋亡性死亡。然而，目前尚不清楚神经营养因子和TNF是否协同细胞内信号传导。利用绿色荧光蛋白标记的NF-κ B 1（GFP-NF-KB 1），我们研究了TNF-α和神经营养因子对PC 12细胞中NF-κ B核转位的影响。TNF-α诱导GFP-NF-KB 1在60 min内逐渐从胞浆转位至胞核。蛋白酶体特异性抑制剂lactacystin预处理显著抑制TNF-α刺激后GFP-NF-KB 1的核转位。此外，我们发现，TNF-α和神经营养因子如神经生长因子（NGF）和脑源性神经营养因子（BDNF）的共刺激大大增加了GFP-NF-B1的核转位，而NGF和BDNF本身都不诱导转位。这些结果表明，通过TNF受体和神经营养因子受体的信号转导途径对NF-κ B的活化之间存在密切的相关性，并且NGF和BDNF增强TNF-α诱导的NF-κ B的核转位。阿尔法2005爱思唯尔爱尔兰有限公司保留所有权利。
Neurotrophic factors regulate neuronal survival and differentiation and control neurite outgrowth by binding to tyrosine kinase receptors, the Trks, and a tumor necrosis factor (TNF) receptor-like molecule, p75 neurotrophin receptor. A proinflammatory cytokine, TNF, also affects survival and apoptotic death in neuronal cells. However, it is still unclear whether neurotrophic factors and TNF co-operate the intracellular signaling. Using green fluorescent protein-tagged NF-KBI (GFP-NF-KB1), we examined here the effects of TNF-alpha and neurotrophic factors on the nuclear translocation of NF-KB in PC12 cells. TNF-alpha induced gradually the translocation of GFP-NF-KB1 from the cytoplasm to the nucleus within 60 min. Pretreatment of lactacystin which is a proteasome-specific inhibitor suppressed significantly the nuclear translocation of GFP-NF-KB1 after TNF-alpha stimulation. In addition, we found that co-stimulation of TNF-alpha and neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) increased greatly the nuclear translocation of GFP-NF-B1 whereas neither NGF nor BDNF itself induced the translocation. These results suggested that there is a close correlation between the signaling pathways via TNF receptors and neurotrophin receptors for the NF-KB activation, and that NGF and BDNF enhance TNF-alpha-induced nuclear translocation of NF-KB. alpha 2005 Elsevier Ireland Ltd. All rights reserved.