title: Sustained phosphorylation of mitogen-activated protein kinase is required for basic fibroblast growth factor-mediated axonal branch formation in cultured rat hippocampal neurons.
abstract: Basic fibroblast growth factor (bFGF) has been reported to promote the formation of axonal branches in cultured brain neurons. In the present study, we investigated whether the mitogen-activated protein kinase (MAPK) cascade was involved in this action of bFGF in cultured rat hippocampal neurons. Recombinant human bFGF (0.1-10 ng/ml) induced phosphorylation of p44/42 MAPK in a concentration and time-dependent manner. The phosphorylation of p44/42 MAPK occurred rapidly within 5 min after addition of bFGF, and lasted for 48 h. The bFGF-induced phosphorylation of p44/42 MAPK and axonal branch formation were both blocked by simultaneous addition of U0126 and PD98059, specific inhibitors of MAPK kinases. Furthermore, when U0126 and PD98059 were added 24 h after bFGF, phosphorylation of p44/42 m MAPK was decreased, and axonal branch formation was stopped. These results suggest that sustained activation of the MAPK cascade is required for bFGF-mediated axonal branch formation.
authors.affiliation: Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, The University of Tokyo, 113-0033, Tokyo, Japan. abe@hoshi.ac.jp
authors.forename: K
authors.initials: K
authors.lastname: Abe
authors.forename: A
authors.initials: A
authors.lastname: Aoyagi
authors.forename: H
authors.initials: H
authors.lastname: Saito
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002070:Butadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D009570:Nitriles; D011994:Recombinant Proteins; C113580:U 0126; D016222:Fibroblast Growth Factor 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one