...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >Expression and function of striatal enriched protein tyrosine phosphatase is profoundly altered in cerebral ischemia.
【24h】

Expression and function of striatal enriched protein tyrosine phosphatase is profoundly altered in cerebral ischemia.

机译：纹状体富集蛋白酪氨酸磷酸酶的表达和功能在脑缺血中发生了深刻的改变。

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

Striatal enriched protein tyrosine phosphatase (STEP) acts in the central nervous system to dephosphorylate a number of important proteins involved in synaptic function including ERK and NMDA receptor subunits. These proteins are also linked to stroke, in which cerebral ischemia triggers a complex cascade of events. Here we demonstrate that STEP is regulated at both the transcriptional and the post-transcriptional levels in rat models of cerebral ischemia and that its regulation may play a role in the outcome of ischemic insults. After transient middle cerebral artery occlusion, there are profound decreases in the levels of STEP mRNA, whilst in global ischemia STEP mRNA is selectively down-regulated in areas susceptible to ischemic damage. In a neuroprotective preconditioning paradigm, and in regions of the brain that are relatively resistant to ischemic damage, STEP mRNA levels are increased. Furthermore, there is a significant processing of STEP after ischemia to generate a novel species, STEP(33), resulting in a redistribution of STEP from membrane-bound to soluble compartments. Concomitant with the cleavage of mature forms of STEP, there are changes in the phosphorylation state of ERK. We show that the cleavage of STEP leads to a catalytically active form, but this cleaved form no longer binds to and dephosphorylates its substrate pERK. Therefore, in response to ischemic insults, there are profound reductions in both the amount and the activity of STEP, its localization, as well as the activity of one of its key substrates, pERK. These changes in STEP may reflect a critical role in the outcomes of ischemic brain injury.
机译：纹状体富集的蛋白酪氨酸磷酸酶（STEP）在中枢神经系统中起作用，以使许多涉及突触功能的重要蛋白（包括ERK和NMDA受体亚基）脱磷酸化。这些蛋白质也与中风有关，其中脑缺血触发一系列复杂的事件。在这里，我们证明，STEP在大鼠脑缺血模型中在转录水平和转录后水平均受到调节，并且其调节可能在缺血性损伤的结果中起作用。在短暂性大脑中动脉闭塞后，STEP mRNA的水平明显降低，而在整体缺血中，在易受缺血性损伤的区域，STEP mRNA选择性下调。在神经保护性预处理范例中，在相对抗缺血性损伤的大脑区域中，STEP mRNA水平增加。此外，缺血后对STEP进行了大量处理以生成新物种STEP（33），从而导致STEP从膜结合区重新分配到可溶性区室。随着STEP成熟形式的裂解，ERK的磷酸化状态发生变化。我们表明，STEP的切割导致催化活性形式，但这种切割形式不再结合并使其底物pERK去磷酸化。因此，响应缺血性损伤，STEP的数量和活性，其定位以及其关键底物之一pERK的活性都大大降低。 STEP的这些变化可能反映出缺血性脑损伤的结果中的关键作用。

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