...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>EBioMedicine >Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury
【24h】

Uncoupling protein 1 inhibits mitochondrial reactive oxygen species generation and alleviates acute kidney injury

机译：解偶联蛋白1抑制线粒体活性氧的产生并减轻急性肾损伤

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

摘要

Background Uncoupling protein 1 (UCP1) is predominantly found in brown adipose tissue mitochondria, and mediates energy dissipation to generate heat rather than ATP via functional mitochondrial uncoupling. However, little is known about its expression and function in kidney. Methods We carried out a mRNA microarray analysis in mice kidneys with ischemia reperfusion (IR) injury. The most dramatically downregulated gene UCP1 after IR was identified, and its role in generation of mitochondrial reactive oxygen species (ROS) and oxidative stress injury was assessed both in vitro and in vivo. Genetic deletion of UCP1 was used to investigate the effects of UCP1 on ischemia or cisplatin-indued acute kidney injury (AKI) in mice. Findings UCP1 was located in renal tubular epithelial cells in kidney and downregulated in a time-dependent manner during renal IR. Deletion of UCP1 increased oxidative stress in kidneys and aggravated ischemia or cisplatin induced AKI in mice.Viral-based overexpression of UCP1 reduced mitochondrial ROS generation and apoptosis in hypoxia-treated tubular epithelial cells. Furthermore, UCP1 expression was regulated by peroxisome proliferator-activator receptor (PPAR) γ in kidneys during renal IR. Overexpression of PPAR-γ resembled UCP1-overexpression phenotype in vitro. Treatment with PPAR-γ agonist could induce UCP1 upregulation and provide protective effect against renal IR injury in UCP1sup+/+/supmice, but not in UCP1sup?/?/supmice. Interpretation UCP1 protects against AKI likely by suppressing oxidative stress, and activation of UCP1 represents a potential therapeutic strategy for AKI. Fund National Natural Science Foundation of China grants, Science and Technology Commission of Shanghai.
机译：背景解偶联蛋白1（UCP1）主要存在于棕色脂肪组织线粒体中，并介导能量耗散以通过功能性线粒体解偶联而不是ATP产生热量。然而，对其在肾脏中的表达和功能了解甚少。方法我们对缺血再灌注（IR）小鼠肾脏进行了mRNA微阵列分析。鉴定出IR后最显着下调的基因UCP1，并在体内和体外评估了其在线粒体活性氧（ROS）生成和氧化应激损伤中的作用。使用UCP1的基因缺失来研究UCP1对小鼠局部缺血或顺铂引起的急性肾损伤（AKI）的影响。结果UCP1位于肾脏的肾小管上皮细胞中，在肾脏IR期间呈时间依赖性下调。删除UCP1会增加肾脏的氧化应激，并加重缺血或顺铂诱发的AKI小鼠。基于病毒的UCP1过表达减少了缺氧处理后的肾小管上皮细胞的线粒体ROS生成和凋亡。此外，在肾脏IR期间，肾脏中的过氧化物酶体增殖物激活剂受体（PPAR）γ调节UCP1的表达。在体外，PPAR-γ的过表达类似于UCP1的过表达表型。 PPAR-γ激动剂的治疗可诱导UCP1 + / + 小鼠而不是UCP1 ？/？小鼠对UCP1上调，对肾脏IR损伤具有保护作用。解释UCP1可能通过抑制氧化应激来防御AKI，并且UCP1的激活代表AKI的潜在治疗策略。基金获得国家自然科学基金资助，上海市科学技术委员会。

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