...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Circulation research: a journal of the American Heart Association >Broad suppression of NADPH oxidase activity exacerbates ischemia/reperfusion injury through inadvertent downregulation of hypoxia-inducible factor-1α and upregulation of peroxisome proliferator-activated receptor-α
【24h】

Broad suppression of NADPH oxidase activity exacerbates ischemia/reperfusion injury through inadvertent downregulation of hypoxia-inducible factor-1α and upregulation of peroxisome proliferator-activated receptor-α

机译：NADPH氧化酶活性的广泛抑制通过低氧诱导因子-1α的下调和过氧化物酶体增殖物激活的受体-α的上调加重了缺血/再灌注损伤

获取原文
获取原文并翻译 | 示例
   

获取外文期刊封面封底 >>

       
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

RATIONALE: NADPH oxidase (Nox) 2 and Nox4 are major components of the Nox family which purposefully produce reactive oxidative species, namely O 2 - and H2O2, in the heart. The isoform-specific contribution of Nox2 and Nox4 to ischemia/reperfusion (I/R) injury is poorly understood. OBJECTIVE: We investigated the role of Nox2 and Nox4 in mediating oxidative stress and myocardial injury during I/R using loss-of-function mouse models. METHODS AND RESULTS: Systemic (s) Nox2 knockout (KO), sNox4 KO, and cardiac-specific (c) Nox4 KO mice were subjected to I/R (30 minutes/24 hours, respectively). Both myocardial infarct size/area at risk and O2 - production were lower in sNox2 KO, sNox4 KO, and cNox4 KO than in wild-type mice. Unexpectedly, however, the myocardial infarct size/area at risk was greater, despite less O2 - production, in sNox2 KO+cNox4 KO (double-KO) mice and transgenic mice (Tg) with cardiac-specific expression of dominant-negative Nox, which suppresses both Nox2 and Nox4, than in wild-type or single KO mice. Hypoxia-inducible factor-1α was downregulated whereas peroxisome proliferator-activated receptor-α was upregulated in Tg-dominant-negative Nox mice. A cross with mice deficient in prolyl hydroxylase 2, which hydroxylates hypoxia-inducible factor-1α, rescued the I/R injury and prevented upregulation of peroxisome proliferator-activated receptor-α in Tg-dominant-negative Nox mice. A cross with peroxisome proliferator-activated receptor-α KO mice also attenuated the injury in Tg- dominant-negative Nox mice. CONCLUSIONS: Both Nox2 and Nox4 contribute to the increase in reactive oxidative species and injury by I/R. However, low levels of reactive oxidative species produced by either Nox2 or Nox4 regulate hypoxia-inducible factor-1α and peroxisome proliferator-activated receptor-α, thereby protecting the heart against I/R, suggesting that Noxs also act as a physiological sensor for myocardial adaptation.
机译：理由：NADPH氧化酶（Nox）2和Nox4是Nox家族的主要成分，目的是在心脏中产生反应性氧化物质，即O 2-和H2O2。人们对Nox2和Nox4对缺血/再灌注（I / R）损伤的同工型特异性贡献知之甚少。目的：我们使用功能丧失的小鼠模型调查了Nox2和Nox4在I / R介导氧化应激和心肌损伤中的作用。方法和结果：对系统性Nox2基因敲除（KO），sNox4 KO和心脏特异性（c）Nox4 KO小鼠进行I / R（分别为30分钟/ 24小时）。 sNox2 KO，sNox4 KO和cNox4 KO的心肌梗塞面积/危险区域和O2产生均低于野生型小鼠。然而，出乎意料的是，尽管sNox2 KO + cNox4 KO（double-KO）小鼠和心脏特异性表达显性负性Nox的转基因小鼠（Tg）的O2产生量少，但心肌梗塞面积/危险区域更大，尽管与野生型或单KO小鼠相比，它能同时抑制Nox2和Nox4。在Tg显性阴性的Nox小鼠中，低氧诱导因子1α被下调，而过氧化物酶体增殖物激活的受体-α被上调。与缺乏脯氨酰羟化酶2的小鼠杂交，羟化缺氧诱导因子1α，挽救了I / R损伤，并防止了Tg显性阴性Nox小鼠中过氧化物酶体增殖物激活受体α的上调。与过氧化物酶体增殖物激活的受体-αKO小鼠杂交也可减轻Tg显性阴性Nox小鼠的损伤。结论：Nox2和Nox4都有助于反应性氧化物质的增加和I / R损伤。但是，由Nox2或Nox4产生的低水平活性氧化物质可调节缺氧诱导因子1α和过氧化物酶体增殖物激活的受体-α，从而保护心脏免受I / R的侵害，这表明Noxs还可作为心肌的生理传感器适应。

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