Prolonged enhancement of AP-1 DNA binding by blockade of glutamate uptake in cultured neurons.
Prolonged blockade of glutamate reuptake by the specific inhibitor of glutamate transporters, L-transpyrrolidine-2,4-dicarboxylate (PDC), produces a dramatic decrease in NMDA-induced neurotoxicity in cerebellar granule cell cultures, and is accompanied by a down-regulation of NMDA receptors. We now report that cultured cerebellar granule cells treated with 100 microM PDC for 1, 2, 4, 8, 16 and 24h, respectively, show increased AP-1 DNA-binding activity as measured by electrophoretic mobility shift assay. This effect was blocked by the NMDA receptor antagonist, CGP 37849, indicative of a pivotal role of NMDA receptors in the PDC-evoked enhancement of AP-1 DNA-binding. Our results suggest that AP-1 may be involved in the transcriptional regulation of neuronal adaptation initiated by prolonged inhibition of glutamate reuptake.
Kovács
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AD
Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Cebers
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G
Liljequist
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D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004268:DNA-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000494:pharmacology; D019281:Dimerization; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000493:pharmacokinetics*; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D018808:Transcription Factor AP-1 / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*
D004268:DNA-Binding Proteins; D003998:Dicarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D014179:Neurotransmitter Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011759:Pyrrolidines; D016194:Receptors, N-Methyl-D-Aspartate; D018808:Transcription Factor AP-1; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; C083486:pyrrolidine-2,4-dicarboxylic acid