• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>IBRO Reports >Protein targeting to glycogen is a master regulator of glycogen synthesis in astrocytes
【24h】

Protein targeting to glycogen is a master regulator of glycogen synthesis in astrocytes

机译：靶向糖原的蛋白质是星形胶质细胞糖原合成的主要调节剂

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The storage and use of glycogen, the main energy reserve in the brain, is a metabolic feature of astrocytes. Glycogen synthesis is regulated by Protein Targeting to Glycogen (PTG), a member of specific glycogen-binding subunits of protein phosphatase-1 (PPP1). It positively regulates glycogen synthesis through de-phosphorylation of both glycogen synthase (activation) and glycogen phosphorylase (inactivation). In cultured astrocytes, PTG mRNA levels were previously shown to be enhanced by the neurotransmitter noradrenaline. To achieve further insight into the role of PTG in the regulation of astrocytic glycogen, its levels of expression were manipulated in primary cultures of mouse cortical astrocytes using adenovirus-mediated overexpression of tagged-PTG or siRNA to downregulate its expression. Infection of astrocytes with adenovirus led to a strong increase in PTG expression and was associated with massive glycogen accumulation (100 fold), demonstrating that increased PTG expression is sufficient to induce glycogen synthesis and accumulation. In contrast, siRNA-mediated downregulation of PTG resulted in a 2-fold decrease in glycogen levels. Interestingly, PTG downregulation strongly impaired long-term astrocytic glycogen synthesis induced by insulin or noradrenaline. Finally, these effects of PTG downregulation on glycogen metabolism could also be observed in cultured astrocytes isolated from PTG-KO mice. Collectively, these observations point to a major role of PTG in the regulation of glycogen synthesis in astrocytes and indicate that conditions leading to changes in PTG expression will directly impact glycogen levels in this cell type.
机译：糖原（大脑中的主要能量储备）的存储和使用是星形胶质细胞的代谢特征。糖原的合成受靶向糖原的蛋白质（PTG）的调节，PTG是蛋白质磷酸酶1（PPP1）的特定糖原结合亚基的成员。它通过糖原合酶（激活）和糖原磷酸化酶（失活）的去磷酸化来积极调节糖原合成。在培养的星形胶质细胞中，以前显示神经递质去甲肾上腺素能增强PTG mRNA的水平。为了进一步了解PTG在调节星形胶质糖原中的作用，使用腺病毒介导的标记过的PTG或siRNA的过表达来下调PTG的表达，从而在小鼠皮质星形胶质细胞的原代培养物中操纵了PTG的表达水平。用腺病毒感染星形胶质细胞会导致PTG表达强烈增加，并与大量糖原积累（> 100倍）相关，这表明增加的PTG表达足以诱导糖原合成和积累。相反，siRNA介导的PTG下调导致糖原水平降低2倍。有趣的是，PTG的下调强烈损害了胰岛素或去甲肾上腺素诱导的长期星形细胞糖原合成。最后，PTG下调对糖原代谢的这些作用也可以在从PTG-KO小鼠中分离得到的星形胶质细胞中观察到。总的来说，这些观察结果表明PTG在星形胶质细胞中糖原合成的调节中起主要作用，并表明导致PTG表达改变的条件将直接影响该细胞类型中糖原的水平。

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