• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Genes to cells : >Balance between cAMP and Ca2+ signals regulates expression levels of pituitary adenylate cyclase-activating polypeptide gene in neurons
【24h】

Balance between cAMP and Ca2+ signals regulates expression levels of pituitary adenylate cyclase-activating polypeptide gene in neurons

机译：cAMP和Ca2 +信号之间的平衡调节神经元垂体腺苷酸环化酶激活多肽基因的表达水平

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Mice lacking the gene encoding pituitary adenylate cyclase-activating polypeptide (PACAP) or its specific receptor, PAC1, show abnormal behaviors related to schizophrenia. However, the regulation of PACAP expression in neurons remains unclear. Here, we report that Pacap mRNA levels are regulated transcriptionally and post-transcriptionally by cAMP and Ca2+ signals in cultured rat cortical cells. Pacap mRNA levels decreased proportionately with the intensity of cAMP signaling, and this decrease was accelerated by N-methyl-D-aspartate (NMDA) receptor blockade, suggesting that cAMP signaling enhances the degradation of Pacap mRNA, whereas NMDA receptor-mediated signals inhibit its degradation. However, depolarization (which produced a robust increase in Ca2+ signals) together with cAMP signaling resulted in a synergistic induction of Pacap mRNA through calcineurin and its substrate, cAMP-response element-binding protein (CREB)-regulated transcription coactivator 1. These results strongly support the concept that while cAMP signaling can accelerate the degradation of Pacap mRNA, it can also synergistically enhance Ca2+ signaling-induced transcriptional activation of Pacap. Taken together, our findings suggest that a balance between Ca2+ and cAMP signals regulates PACAP levels in neurons and that a perturbation of this balance may result in psychiatric disorders, such as schizophrenia.
机译：缺乏编码垂体腺苷酸环化酶激活多肽（PACAP）或其特定受体PAC1的基因的小鼠表现出与精神分裂症有关的异常行为。但是，尚不清楚神经元中PACAP表达的调控。在这里，我们报道Pacap mRNA水平在培养的大鼠皮质细胞中受到cAMP和Ca2 +信号的转录和转录后调控。 Pacap mRNA的水平随cAMP信号强度的增加而成比例地下降，并且N-甲基-D-天冬氨酸（NMDA）受体阻滞促进了这种下降，这表明cAMP信号增强了Pacap mRNA的降解，而NMDA受体介导的信号抑制了其降解。但是，去极化（在Ca2 +信号中产生了强劲的增加）与cAMP信号一起导致通过钙调神经磷酸酶及其底物，cAMP反应元件结合蛋白（CREB）调控的转录共激活因子1协同诱导Pacap mRNA。支持cAMP信号传导可以加速Pacap mRNA降解的概念，但它也可以协同增强Ca2 +信号传导诱导的Pacap转录激活。综上所述，我们的发现表明，Ca2 +和cAMP信号之间的平衡调节神经元中的PACAP水平，并且这种平衡的扰动可能导致精神疾病，例如精神分裂症。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号