• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>American Journal of Physiology >Involvement of the mitogen-activated protein kinase cascade in peroxynitrite-mediated arachidonic acid release in vascular smooth muscle cells.
【24h】

Involvement of the mitogen-activated protein kinase cascade in peroxynitrite-mediated arachidonic acid release in vascular smooth muscle cells.

机译：有丝分裂原激活的蛋白激酶级联参与过氧亚硝酸盐介导的花生四烯酸在血管平滑肌细胞中的释放。

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

Eicosanoid production is reduced when the nitric oxide (NO.) pathway is inhibited or when the inducible NO synthase gene is deleted, indicating that the NO. and arachidonic acid pathways are linked. We hypothesized that peroxynitrite, formed by the reaction of NO. and superoxide anion, may cause signaling events leading to arachidonic acid release and subsequent eicosanoid generation. Western blot analysis of rat arterial smooth muscle cells demonstrated that peroxynitrite (100-500 microM) and 3-morpholinosydnonimine (SIN-1; 200 microM) stimulate phosphorylation of extracellular signal-regulated kinase (ERK), p38, and cytosolic phospholipase A(2) (cPLA(2)). We found that peroxynitrite-induced arachidonic acid release was completely abrogated by the mitogen-activated protein/ERK kinase (MEK) inhibitor U0126 and by calcium chelators. With the p38 inhibitor SB-20219, we demonstrated that peroxynitrite-induced p38 phosphorylation led to minor arachidonic acid release, whereas U0126 completely blocked p38 phosphorylation. Addition of arachidonic acid caused p38 phosphorylation, suggesting that arachidonic acid or its metabolites are responsible for p38 activation. KN-93, a specific inhibitor of Ca(2+)/calmodulin-dependent kinase II (CaMKII), revealed no role for this kinase in peroxynitrite-induced arachidonic acid release in our cell system. Together, these results show that in response to peroxynitrite the cell initiates the MEK/ERK cascade leading to cPLA(2) activation and arachidonic acid release. Thus studies investigating the role of the NO. pathway on eicosanoid production must consider the contribution of signaling pathways initiated by reactive nitrogen species. These findings may provide evidence for a new role of peroxynitrite as an important reactive nitrogen species in vascular disease.
机译：当一氧化氮（NO。）途径受到抑制或诱导型NO合酶基因缺失时，类花生酸的产生减少。与花生四烯酸途径相连。我们假设过氧亚硝酸盐是由NO反应形成的。和超氧阴离子可能会导致信号传导事件，导致花生四烯酸释放和随后的类花生酸生成。对大鼠动脉平滑肌细胞的蛋白质印迹分析表明，过氧亚硝酸盐（100-500 microM）和3-吗啉代亚胺（SIN-1; 200 microM）刺激细胞外信号调节激酶（ERK），p38和胞质磷脂酶A的磷酸化（2 ）（cPLA（2））。我们发现，有丝分裂原激活的蛋白/ ERK激酶（MEK）抑制剂U0126和钙螯合剂完全废除了过氧亚硝酸盐诱导的花生四烯酸释放。使用p38抑制剂SB-20219，我们证明了过亚硝酸盐诱导的p38磷酸化导致少量花生四烯酸释放，而U0126则完全阻断了p38磷酸化。花生四烯酸的添加引起p38磷酸化，表明花生四烯酸或其代谢产物负责p38的活化。 KN-93，一种特定的Ca（2 +）/钙调蛋白依赖性激酶II（CaMKII）抑制剂，显示该激酶在过氧亚硝酸盐诱导的花生四烯酸释放在我们的细胞系统中没有作用。在一起，这些结果表明，响应过氧亚硝酸盐的细胞引发MEK / ERK级联，导致cPLA（2）激活和花生四烯酸释放。因此，研究调查了NO的作用。类花生酸生产的途径必须考虑反应性氮物种引发的信号传导途径的贡献。这些发现可能为过氧亚硝酸盐作为血管疾病中重要的反应性氮物种的新作用提供证据。

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