Glutamate regulates Oct-2 DNA-binding activity through alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors in cultured chick Bergmann glia cells.
Ionotropic glutamate receptors in cerebellar Bergmann glial cells are linked to transcriptional regulation and, by these means, are thought to play an important role in plasticity, learning and memory and in several neuropathologies. Within the CNS, the transcription factors of the POU family bind their target DNA sequences after a growth factor-dependent phosphorylation-dephosphorylation cascade. Exposure of cultured Bergmann glial cells to glutamate leads to a time- and dose-dependent increase in Oct-2 DNA-binding activity. The use of specific pharmacological tools established the involvement of Ca2+-permeable alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors. Furthermore, the signaling cascade includes phosphatidyl inositol 3-kinase as well as protein kinase C activation. Interestingly, transcriptional as well as translational inhibitors abolish the glutamate effect, suggesting a transcriptional up-regulation of the oct-2 gene. These data demonstrate that Oct-2 expression is not restricted to neurons and further strengthen the notion that the glial glutamate receptors participate in the modulation of glutamatergic cerebellar neurotransmission.
Méndez
J Alfredo
JA
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del instituto Politécnico Nacional, México.
López-Bayghen
Esther
E
Rojas
Fausto
F
Hernández
María Elena
ME
Ortega
Arturo
A
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002273:Carcinogens / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007555:Isoxazoles / Q000494:pharmacology*; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D050813:Octamer Transcription Factor-2; D011233:Precipitin Tests / Q000379:methods; D011422:Propionates / Q000494:pharmacology*; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism*; D037941:Silencer Elements, Transcriptional / Q000235:genetics / Q000502:physiology; D013687:Telencephalon / Q000166:cytology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
D002273:Carcinogens; D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D050813:Octamer Transcription Factor-2; C058435:POU2F2 protein, human; D011422:Propionates; D017470:Receptors, Glutamate; D014157:Transcription Factors; C081662:alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate; D018698:Glutamic Acid; D013755:Tetradecanoylphorbol Acetate