...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Novel plasminogen activator inhibitor-1-derived peptide protects against impairment of cerebrovasodilation after photothrombosis through inhibition of JNK MAPK.
【24h】

Novel plasminogen activator inhibitor-1-derived peptide protects against impairment of cerebrovasodilation after photothrombosis through inhibition of JNK MAPK.

机译：新型纤溶酶原激活物抑制剂-1衍生肽通过抑制JNK MAPK防止光栓塞后脑血管舒张功能受损。

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

The sole FDA-approved treatment for acute stroke is recombinant tissue-type plasminogen activator (rtPA). However, rtPA aggravates the impairment of cerebrovasodilation induced by global hypoxia/ischemia; this impairment is attenuated by the preinjury treatment with the plasminogen activator inhibitor derivative EEIIMD. MAPK (a family of kinases, p38, and JNK) is upregulated after cerebral ischemia. In this study, we determined whether the novel plasminogen activator inhibitor-derived peptide, Ac-RMAPEEIIMDRPFLYVVR-amide, (PAI-1-DP) given 30 min before or 2 h after, focal central nervous system injury induced by photothrombosis would preserve responses to cerebrovasodilators and the role of p38 and JNK MAPK in such effects. Cerebrospinal fluid JNK and p38 levels were elevated by photothrombotic injury, an effect potentiated by rtPA. Cerebrovasodilation was blunted by photothrombosis and reversed to vasoconstriction by rtPA but restored to dilation by PAI-1-DP pre- and posttreatment. PAI-1-DP blocked JNK, but preserved p38 MAPK upregulation after photothrombosis. The JNK MAPK antagonist SP600125 prevented, and the p38 antagonist SB203580 potentiated, impaired cerebrovasodilation after photothrombosis. These data indicate that rtPA impairs cerebrovasodilation after injury by activating JNK, while p38 MAPK is protective, and that the novel peptide PAI-1-DP protects by inhibiting activation of JNK by rtPA. JNK MAPK inhibitors, including PAI-1-DP, may offer a novel approach to increase the benefit-to-risk ratio of thrombolytic therapy and enable its use in central nervous system ischemic disorders.
机译：FDA批准的急性中风的唯一治疗方法是重组组织型纤溶酶原激活剂（rtPA）。然而，rtPA加重了由整体性缺氧/局部缺血引起的脑血管舒张功能的损害。通过用纤溶酶原激活物抑制剂衍生物EEIIMD进行损伤前治疗，可减轻这种损害。脑缺血后，MAPK（激酶，p38和JNK家族）被上调。在这项研究中，我们确定了由纤溶酶原激活物抑制剂衍生的肽Ac-RMAPEEIIMDRPFLYVVR-酰胺（PAI-1-DP）在由血栓形成引起的局灶性中枢神经系统损伤之前或之后30分钟给予，能否保留对脑血管扩张剂以及p38和JNK MAPK的作用在此类作用中。血栓性损伤可升高脑脊液JNK和p38的水平，rtPA可以增强这种作用。脑血栓形成因光血栓形成而钝化，并由rtPA逆转为血管收缩，但在PAI-1-DP治疗前后均恢复为扩张状态。 PAI-1-DP阻断了JNK，但在光栓形成后保留了p38 MAPK上调。在血栓形成后，JNK MAPK拮抗剂SP600125得以预防，而p38拮抗剂SB203580增强了脑血管舒张功能。这些数据表明，rtPA通过激活JNK损害了损伤后的脑血管舒张作用，而p38 MAPK具有保护作用，而新型肽PAI-1-DP通过抑制rtPA激活JNK的活性来进行保护。 JNK MAPK抑制剂，包括PAI-1-DP，可能提供一种新颖的方法来增加溶栓治疗的获益比，并使其可用于中枢神经系统缺血性疾病。

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