首页> 外文期刊>Cellular Signalling >Hsp90 inhibitors induce the unfolded protein response in bovine and mice lung cells
【24h】

Hsp90 inhibitors induce the unfolded protein response in bovine and mice lung cells

机译:HSP90抑制剂诱导牛和小鼠肺细胞中展开的蛋白质反应

获取原文
获取原文并翻译 | 示例
       

摘要

The unfolded protein response element protects against endoplasmic reticulum stress and delivers protection towards potentially harmful challenges. The components of this multi-branch molecular machinery, namely the protein kinase RNA-like ER kinase, the activating transcription factor 6, and the inositol-requiring enzyme-la; expand the endoplasmic reticulum capacity to support cellular function under stress conditions. In the present study, we employed bovine pulmonary aortic endothelial cells and mice to investigate the possibility that the Hsp90 inhibitors Tanespimycin (17-AAG) and Luminespib (AUY-922) exert the capacity to trigger the unfolded protein response. The induction of the unfolded protein response regulators immunoglobulin heavy-chainbinding protein, endoplasmic reticulum oxidoreductin-1 alpha; and protein disulfide isomerase was also examined. It appears that both inhibitors capacitate the induction of the unfolded protein response element in vitro, since lung cells exposed to 1, 2 and 10 mu M of 17-AAG or AUY-922 for 4, 6, 8, 16 and 48 h demonstrated increased levels of those proteins. Similar events occurred in the lungs of mice treated with AUY-922. Thus, our study demonstrates that Hsp90 inhibition triggers the activities of the unfolded protein response, and suggests that this molecular machinery contributes in the protective action of Hsp90 inhibitors in the lung micro-vasculature.
机译:展开的蛋白质反应元件可保护内质网应力,并为潜在有害挑战提供保护。该多分支分子机械的组分,即蛋白激酶RNA样ER激酶,活化转录因子6和肌醇需要酶-1a;扩大内质网容量以支持压力条件下的细胞功能。在本研究中,我们使用牛肺主动脉内皮细胞和小鼠来研究HSP90抑制剂TANESPIMYCIN(17-AAG)和LUMINEPIB(AUY-922)施加能力以引发展开蛋白质反应的可能性。展开蛋白反应调节剂免疫球蛋白重链蛋白,内质网氧化素-1α的诱导;还检查了蛋白质二硫键异构酶。似乎两种抑制剂在体外容量诱导展开的蛋白质反应元件,因为暴露于1,2和10μm的17-AAG或Auy-922的1,6,8,16和48小时,所示的肺细胞增加这些蛋白质的水平。用Auy-922处理的小鼠的肺部发生类似的事件。因此,我们的研究表明,HSP90抑制触发了展开蛋白质反应的活性,并表明该分子机制有助于HSP90抑制剂在肺部微脉管系统中的保护作用。

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