• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Drug Target Insights >Hsp60 Chaperonin Acts as Barrier to Pharmacologically Induced Oxidative Stress Mediated Apoptosis in Tumor Cells with Differential Stress Response
【24h】

Hsp60 Chaperonin Acts as Barrier to Pharmacologically Induced Oxidative Stress Mediated Apoptosis in Tumor Cells with Differential Stress Response

机译：Hsp60伴侣蛋白充当药理学诱导的氧化应激介导的具有不同应激反应的肿瘤细胞凋亡的屏障。

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

摘要

Mitochondrial functions play a central role in energy metabolism and provide survival fitness to both normal and tumor cells. Mitochondrial chaperonin Hsp60 is involved in both pro- and anti-apoptotic functions, but how Hsp60 senses the mitochondria selective oxidative stress response is unknown. In this study, by using rotenone, an irreversible inhibitor of oxidative phosphorylation against IMR-32 and BC-8 tumor cells containing differential heat shock transcriptional machinery, we studied whether the oxidative stress response is related to Hsp60. The accelerated cytotoxicity in response to rotenone has been correlated with enhanced production of O2●–, H2O2, reactive oxygen species, and Hsp60 translocation from the mitochondria to the cytoplasm. The inability of cells to resist oxidative stress mediated Hsp60 translocation appeared to depend on mitochondrial oxyradical scavenging system and Bax translocation. A delayed oxidative stress response in hsp60 shRNA-treated cells was found to be due to increased mitochondrial translocation of Hsp60 on shRNA pre-sensitization. Overexpression of Hsp60 failed to protect cells from oxidative stress due to a lack of its mitochondrial retention upon post-rotenone treatment. These results also revealed that Hsp60 mitochondrial localization is indispensable for decreasing O2●– levels, but not H2O2 and ROS levels. However, cycloheximide treatment alone induced Hsp60 translocation, while rotenone combination delayed this translocation. In contrast to oxidative stress, MG132 and 17AAG treatments showed mitochondrial retention of Hsp60; however, MG132 combination either with hsp60 shRNA or 17AAG induced its translocation. Additionally, overexpression of Huntingtin gene also resulted in Hsp60 mitochondrial accumulation. We suggest that Hsp60 may act as a barrier to pharmacological targeting of mitochondria.
机译：线粒体功能在能量代谢中发挥重要作用，并为正常细胞和肿瘤细胞提供生存适应性。线粒体伴侣蛋白Hsp60参与促凋亡和抗凋亡功能，但是Hsp60如何感知线粒体选择性氧化应激反应尚不清楚。在这项研究中，通过使用鱼藤酮，鱼藤酮是一种针对包含不同热休克转录机制的IMR-32和BC-8肿瘤细胞的不可逆的氧化磷酸化抑制剂，我们研究了氧化应激反应是否与Hsp60相关。响应鱼藤酮的加速细胞毒性与O2●–，H2O2，活性氧和Hsp60从线粒体到细胞质易位的产生有关。细胞不能抵抗氧化应激介导的Hsp60易位似乎取决于线粒体的氧自由基清除系统和Bax易位。发现在hsp60 shRNA处理的细胞中延迟的氧化应激反应是由于shRNA预敏化时Hsp60的线粒体转运增加所致。 Hsp60的过表达不能保护细胞免受氧化应激，因为在鱼藤酮处理后缺乏线粒体保留。这些结果还表明，Hsp60线粒体定位对于降低O2•–水平不可或缺，但对于H2O2和ROS水平却不可。但是，单独使用环己酰亚胺治疗可诱导Hsp60易位，而鱼藤酮组合可延迟这种易位。与氧化应激相反，MG132和17AAG处理显示Hsp60的线粒体保留。然而，MG132与hsp60 shRNA或17AAG的结合可诱导其易位。此外，Huntingtin基因的过表达也导致Hsp60线粒体积累。我们建议Hsp60可能充当线粒体药理靶向的障碍。

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