Neurotrophic effect of basic fibroblast growth factor is mediated by the p42/p44 mitogen-activated protein kinase cascade in cultured rat cortical neurons.
Basic fibroblast growth factor (bFGF) has been reported to support the survival of brain neurons. In the present study, we investigated whether the neurotrophic effect of bFGF is mediated by the mitogen-activated protein kinase (MAPK) cascade in cultured rat cerebral cortical neurons. Recombinant human bFGF (0.1-10 ng/ml) induced phosphorylation of p44/42 MAPK (ERK1/2) in a concentration- and time-dependent manner. bFGF-induced ERK1/2 phosphorylation and promotion of neuronal survival were both blocked by U0126 and PD98059, inhibitors of the MAPK-activating enzyme MEK. These results suggest that the MEK/ERK signal transduction cascade is involved in the neurotrophic effect of bFGF.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-0033, Tokyo, Japan. abe@hoshi.ac.jp
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D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar
D016222:Fibroblast Growth Factor 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases