...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Canadian Journal of Physiology and Pharmacology >Redox-dependent MAP kinase signaling by Ang II in vascular smooth muscle cells: role of receptor tyrosine kinase transactivation.
【24h】

Redox-dependent MAP kinase signaling by Ang II in vascular smooth muscle cells: role of receptor tyrosine kinase transactivation.

机译：血管紧张素Ⅱ在血管平滑肌细胞中的氧化还原依赖性MAP激酶信号传导：受体酪氨酸激酶反式激活的作用。

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

We investigated the role of receptor tyrosine kinases in Ang II-stimulated generation of reactive oxygen species (ROS) and assessed whether MAP kinase signaling by Ang II is mediated via redox-sensitive pathways. Production of ROS and activation of NADPH oxidase were determined by DCFDA (dichlorodihydrofluorescein diacetate; 2 micromol/L) fluorescence and lucigenin (5 micromol/L) chemiluminescence, respectively, in rat vascular smooth muscle cells (VSMC). Phosphorylation of ERK1/2, p38MAP kinase and ERK5 was determined by immunoblotting. The role of insulin-like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) was assessed with the antagonists AG1024 and AG1478, respectively. ROS bioavailability was manipulated with Tiron (10(-5) mol/L), an intracellular scavenger, and diphenylene iodinium (DPI; 10(-6) mol/L), an NADPH oxidase inhibitor. Ang II stimulated NADPH oxidase activity and dose-dependently increased ROS production (p < 0.05). These actions were reduced by AG1024 and AG1478. Ang II-induced ERK1/2 phosphorylation (276% of control) was decreased by AG1478 and AG1024. Neither DPI nor tiron influenced Ang II-stimulated ERK1/2 activity. Ang II increased phosphorylation of p38 MAP kinase (204% of control) and ERK5 (278% of control). These effects were reduced by AG1024 and AG1478 and almost abolished by DPI and tiron. Thus Ang II stimulates production of NADPH-inducible ROS partially through transactivation of IGF-1R and EGFR. Inhibition of receptor tyrosine kinases and reduced ROS bioavaliability attenuated Ang II-induced phosphorylation of p38 MAP kinase and ERK5, but not of ERK1/2. These findings suggest that Ang II activates p38MAP kinase and ERK5 via redox-dependent cascades that are regulated by IGF-1R and EGFR transactivation. ERK1/2 regulation by Ang II is via redox-insensitive pathways.
机译：我们调查了受体酪氨酸激酶在血管紧张素II刺激的活性氧（ROS）生成中的作用，并评估了血管紧张素II是否通过氧化还原敏感途径介导MAP激酶信号传导。在大鼠血管平滑肌细胞（VSMC）中分别通过DCFDA（二氯二氢荧光素二乙酸酯; 2 micromol / L）荧光和发光素（5 micromol / L）化学发光测定ROS的产生和NADPH氧化酶的激活。通过免疫印迹测定ERK1 / 2，p38MAP激酶和ERK5的磷酸化。分别用拮抗剂AG1024和AG1478评估了胰岛素样生长因子1受体（IGF-1R）和表皮生长因子受体（EGFR）的作用。使用细胞内清除剂Tiron（10（-5）mol / L）和NADPH氧化酶抑制剂二亚苯基二碘（DPI; 10（-6）mol / L）处理ROS的生物利用度。 Ang II刺激NADPH氧化酶活性并剂量依赖性地增加ROS的产生（p <0.05）。 AG1024和AG1478减少了这些动作。 AG1478和AG1024降低了Ang II诱导的ERK1 / 2磷酸化（对照组的276％）。 DPI和铁离子均未影响Ang II刺激的ERK1 / 2活性。 Ang II增加p38 MAP激酶（对照组的204％）和ERK5（对照组278％）的磷酸化。 AG1024和AG1478减少了这些影响，而DPI和tiron几乎消除了这些影响。因此，Ang II部分通过IGF-1R和EGFR的反式激活刺激NADPH诱导的ROS的产生。受体酪氨酸激酶的抑制和ROS生物利用度的降低减弱了Ang II诱导的p38 MAP激酶和ERK5的磷酸化，但未减弱ERK1 / 2。这些发现表明，Ang II通过氧化还原依赖性级联激活p38MAP激酶和ERK5，而该级联受IGF-1R和EGFR反式激活。 Ang II对ERK1 / 2的调节是通过对氧化还原不敏感的途径进行的。

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