Neurotrophic factors increase tumor necrosis factor-alpha-induced nuclear translocation of NF-kappaB 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-kappaB1 (GFP-NF-kappaB1), we examined here the effects of TNF-alpha and neurotrophic factors on the nuclear translocation of NF-kappaB in PC12 cells. TNF-alpha induced gradually the translocation of GFP-NF-kappaB1 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-kappaB1 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-kappaB1 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-kappaB activation, and that NGF and BDNF enhance TNF-alpha-induced nuclear translocation of NF-kappaB.
Furuno
Tadahide
T
Graduate School of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Japan.furuno@dpc.aichi-gakuin.ac.jp
Nakanishi
Mamoru
M
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D004338:Drug Combinations; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016716:PC12 Cells / Q000166:cytology; D051381:Rats; D013997:Time Factors; D014162:Transfection / Q000379:methods; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004338:Drug Combinations; D016328:NF-kappa B; D009414:Nerve Growth Factors; D014409:Tumor Necrosis Factor-alpha; D049452:Green Fluorescent Proteins