Neurotrophic factors increase tumor necrosis factor-α-induced nuclear translocation of NF-κB in rat PC12 cells

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-κB1 (GFP-NF-κB1), we examined here the effects of TNF-α and neurotrophic factors on the nuclear translocation of NF-κB in PC12 cells. TNF-α induced gradually the translocation of GFP-NF-κB1 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-κB1 after TNF-α stimulation. In addition, we found that co-stimulation of TNF-α and neurotrophic factors such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) increased greatly the nuclear translocation of GFP-NF-κB1 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-κB activation, and that NGF and BDNF enhance TNF-α-induced nuclear translocation of NF-κB.