...
  • 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 >Evidence for the role of PI(3) -kinase-AKT-eNOS signalling pathway in secondary inflammatory process after spinal cord compression injury in mice.
【24h】

Evidence for the role of PI(3) -kinase-AKT-eNOS signalling pathway in secondary inflammatory process after spinal cord compression injury in mice.

机译：PI（3）-激酶-AKT-eNOS信号通路在小鼠脊髓压迫性损伤继发性炎症过程中的作用的证据。

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

Endothelial nitric oxide synthase (eNOS) is a dynamic enzyme tightly controlled by co- and post-translational lipid modifications, phosphorylation and regulated by protein-protein interactions. In this study we have pharmacologically modulated the activation of eNOS, at different post-translational levels, to assess the role of eNOS-derived NO and regulatory mechanisms in tissue damage associated with spinal cord injury (SCI). SC trauma was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. SCI in mice resulted in severe trauma characterized by oedema, neutrophil infiltration, and production of inflammatory mediators, tissue damage and apoptosis. LY294002, an inhibitor of phosphatidylinositol 3-kinase that initiates Akt-catalysed phosphorylation of eNOS on Ser1179, was administered 1 h before the induction of SCI; 24 h after SCI sections were taken for histological examination and for biochemical studies. In this study we clearly demonstrated that pre-treatment with LY294002 reversed the increased activation of eNOS and Akt observed following SCI, and developed a severe trauma characterized by oedema, tissue damage and apoptosis (measured by TUNEL staining, Bax, Bcl-2 and Fas-L expression). Histological damage also correlated with neutrophil infiltration, assessed as myeloperoxidase activity. Overall these results suggest that activation of the Akt pathway in SC tissue subject to SCI is a protective event, triggered in order to protect the injured tissue through a fine tuning of the endothelial NO pathway.
机译：内皮型一氧化氮合酶（eNOS）是一种动态酶，受共翻译和翻译后脂质修饰，磷酸化和蛋白质-蛋白质相互作用的调控。在这项研究中，我们已在药理学上调节了不同翻译后水平下eNOS的激活，以评估eNOS衍生的NO和调节机制在与脊髓损伤（SCI）相关的组织损伤中的作用。通过四层T5-T8椎板切除术对硬脑膜施加血管夹（24 g力）可诱发SC创伤。小鼠SCI导致严重的外伤，其特征在于水肿，中性粒细胞浸润以及炎性介质的产生，组织损伤和细胞凋亡。 LY294002是磷脂酰肌醇3激酶的抑制剂，可在SCI诱导前1小时施用，该抑制剂可引发Akt催化Ser1179上eNOS的磷酸化。 SCI切片后24小时进行组织学检查和生化研究。在这项研究中，我们清楚地证明了用LY294002进行的预处理逆转了SCI后观察到的eNOS和Akt活化增加，并形成了以水肿，组织损伤和细胞凋亡为特征的严重创伤（通过TUNEL染色，Bax，Bcl-2和Fas测量） -L表达式）。组织学损害也与嗜中性粒细胞浸润相关，评估为髓过氧化物酶活性。总的来说，这些结果表明，受到SCI的SC组织中Akt途径的激活是保护性事件，其触发是为了通过微调内皮NO途径来保护受伤的组织。

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