Méndez J Alfredo, López-Bayghen Esther, Ortega Arturo
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios, Avanzados del Instituto Politécnico Nacional, México.
J Neurosci Res. 2005 Jul 1;81(1):21-30. doi: 10.1002/jnr.20519.
Glutamate, the major excitatory neurotransmitter in the central nervous system, is critically involved in gene expression regulation at the transcriptional and translational levels. Its activity through ionotropic as well as metabotropic receptors modifies the protein repertoire in neurons and glial cells. In avian cerebellar Bergmann glia cells, glutamate receptors trigger a diverse array of signaling cascades that include activity-dependent transcription factors such as the activator protein-1, the cAMP response-element binding protein, and Oct-2. We analyze the upstream regulatory elements involved in Oct-2 activation. Our results demonstrate that Ca2+ influx, protein kinase C, phosphatidylinositol-3 kinase, Src, and nuclear factor (NF)kappaB are involved in this signaling pathway. Our findings link alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor activation to a negative phase of chkbp gene regulation, controlled by NFkappaB.
谷氨酸是中枢神经系统中的主要兴奋性神经递质,在转录和翻译水平的基因表达调控中起着关键作用。其通过离子型和代谢型受体的活性改变神经元和神经胶质细胞中的蛋白质组。在鸟类小脑的伯格曼胶质细胞中,谷氨酸受体触发多种信号级联反应,其中包括活性依赖的转录因子,如激活蛋白-1、cAMP反应元件结合蛋白和Oct-2。我们分析了参与Oct-2激活的上游调控元件。我们的结果表明,Ca2+内流、蛋白激酶C、磷脂酰肌醇-3激酶、Src和核因子(NF)κB参与了该信号通路。我们的发现将α-氨基-3-羟基-5-甲基异恶唑-4-丙酸(AMPA)受体激活与由NFκB控制的chkbp基因调控的负相联系起来。