title: N-methyl-D-aspartate signaling to nuclear activator protein-1 through mechanisms different from those for kainate signaling in murine brain.
abstract: Protein de novo synthesis is mainly under the control at the level of gene transcription by transcription factors in cell nuclei in eukaryotes. The systemic administration of N-methyl-D-aspartate resulted in selective but transient potentiation of binding of a radiolabeled double-stranded oligonucleotide probe for the nuclear transcription factor activator protein-1 in murine hippocampus, without markedly affecting binding of probes for other transcription factors. By contrast, kainic acid induced more potent and more persistent potentiation of activator protein- binding in the hippocampus than N-methyl-D-aspartate. The protein synthesis inhibitor cycloheximide was effective in significantly preventing the potentiation by N-methyl-D-aspartate, but not that by kainic acid at the doses used. Moreover, kainic acid induced much more and longer expression of immunoreactive c-Fos protein in the hippocampus than N-methyl-D-aspartate. However, neither N-methyl-D-aspartate nor kainate induced expression of cyclic AMP response element binding protein phosphorylated at serine133 in the hippocampus from 10 min to 24 h after the administration. Instead, kainate was more potent than N-methyl-D-aspartate in facilitating both dephosphorylation at serine and phosphorylation at tyrosine of particular nuclear proteins in the hippocampus. These results suggest that N-methyl-D-aspartate and kainate signals may be differentially transduced into cell nuclei to express the activator protein-1 complex through molecular mechanisms which differ from phosphorylation of cyclic AMP response element binding protein at serine133 but involve serine dephosphorylation and/or tyrosine phosphorylation of particular nuclear proteins in the murine hippocampus.
authors.affiliation: Department of Pharmacology, Setsunan University, Hirakata, Osaka, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Yoneda
authors.forename: K
authors.initials: K
authors.lastname: Ogita
authors.forename: Y
authors.initials: Y
authors.lastname: Azuma
authors.forename: M
authors.initials: M
authors.lastname: Ikeda
authors.forename: H
authors.initials: H
authors.lastname: Tagami
authors.forename: T
authors.initials: T
authors.lastname: Manabe
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016202:N-Methylaspartate / Q000494:pharmacology*; D015345:Oligonucleotide Probes; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D015345:Oligonucleotide Probes; D018808:Transcription Factor AP-1; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D003513:Cycloheximide; D007608:Kainic Acid