...
  • 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 >Involvement of the Akt-dependent CREB signaling pathway in hydrogen-peroxide-induced early growth response protein-1 expression in rat vascular smooth muscle cells
【24h】

Involvement of the Akt-dependent CREB signaling pathway in hydrogen-peroxide-induced early growth response protein-1 expression in rat vascular smooth muscle cells

机译：AKT依赖性CREB信号传导途径在大鼠血管平滑肌细胞中的过氧化氢诱导的早期生长响应蛋白-1表达中的参与

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

Increased generation of reactive oxygen species is believed to play a key role in the pathophysiology of cardiovascular diseases. Excessive growth and proliferation of vascular smooth muscle cells (VSMCs) have been suggested to be major contributors to vascular dysfunction. Potential involvement of early growth response protein-1 (Egr-1), a zinc finger transcription factor, in the development of vascular diseases has been suggested. Recent studies have shown that the reactive oxygen species hydrogen peroxide (H2O2) increases Egr-1 expression in VSMCs; however, signaling events leading to H2O2-induced Egr-1 expression are not fully understood. Therefore, we aimed to determine the signaling pathways implicated in H2O2-induced Egr-1 expression in rat VSMCs. Pharmacological blockade of the phosphatidylinositol 3-kinase/Akt pathway by wortmannin or SC66 significantly inhibited the protein and mRNA levels of Egr-1 induced by H2O2. H2O2-induced Egr-1 expression was associated with increased phosphorylation of cyclic AMP response element-binding (CREB) protein, and pharmacological inhibition or silencing of Akt attenuated both H2O2-induced CREB phosphorylation and Egr-1 expression. Moreover, RNA interference-mediated depletion of CREB almost completely suppressed the stimulatory effect of H2O2 on Egr-1 expression. Pharmacological blockade or silencing of c-Src resulted in significant suppression of H2O2-induced Egr-1 expression as well as Akt and CREB phosphorylation. These data show that H2O2 enhances the expression of Egr-1, which was associated with increased phosphorylation of Akt, and H2O2 triggers its effects on Egr-1 expression through c-Src-mediated Akt and CREB-dependent signaling events in VSMCs.
机译：据信增加了活性氧物质的产生在心血管疾病的病理生理学中发挥着关键作用。已经提出血管平滑肌细胞（VSMC）的过度生长和增殖是血管功能障碍的主要贡献者。提出了早期生长反应蛋白-1（EGR-1），锌指转录因子，在血管疾病发展中的潜在累及。最近的研究表明，活性氧物质过氧化氢（H2O2）增加了VSMC中的EGR-1表达;然而，导致H2O2诱导的EGR-1表达的信号传导事件尚不完全理解。因此，我们旨在确定在大鼠VSMC中含有H2O2诱导的EGR-1表达的信号传导途径。磷脂酰肌醇3-激酶/ Akt途径的药理阻滞通过Wortmannin或SC66显着抑制了H 2 O 2诱导的EGR-1的蛋白质和mRNA水平。 H 2 O 2诱导的EGR-1表达与循环AMP响应元件结合（CREB）蛋白的磷酸化增加相关，以及AKT的药理学抑制或沉默衰减H2O2诱导的CREB磷酸化和EGR-1表达。此外，RNA干扰介导的CREB的耗竭几乎完全抑制了H2O2对EGR-1表达的刺激作用。 C-SRC的药理阻滞或沉默导致H 2 O 2诱导的EGR-1表达以及Akt和CreB磷酸化的显着抑制。这些数据表明，H 2 O 2增强了EGR-1的表达，其与AKT的磷酸化增加相关，H2O2通过在VSMC中通过C-SRC介导的AKT和CREB依赖性信号传导事件触发其对EGR-1表达的影响。

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