...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Apoptosis >BNip3 is a mediator of TNF-induced necrotic cell death
【24h】

BNip3 is a mediator of TNF-induced necrotic cell death

机译：BNip3是TNF诱导坏死细胞死亡的介体

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

Tumor necrosis factor (TNF) is a pleiotropic cytokine involved in immune modulation, inflammatory reactions, and target cell death in many pathologic conditions. The cell death pathways triggered by TNF include the caspase-8/Bid-dependent apoptotic pathway and the caspase-independent necrosis pathway (necroptosis). While the signaling pathways activated after binding of TNF to the TNF receptor (TNFR) and subsequent insertion of Bid/Bax/Bik into the outer mitochondrial membrane are relatively well known, other cell death pathways and the participating signaling molecules remain to be clarified. BNip3 is a pro-death protein and a member of the BH3-only Bcl-2 family. When ectopically overexpressed or induced by hypoxia, BNip3 induces various types of cell death via mitochondrial or non-mitochondrial death cascades. In this study using A549 alveolar epithelial cells of the lung, we show that BNip3 is transcriptionally and translationally upregulated by TNF, and its expression level determines the sensitivity to necroptosis induced by TNF. However, BNip3 does not appear to be involved in caspase-8/Bid-dependent apoptotic cell death in these alveolar lung cells. Finally, we show that the generation of reactive oxygen species (ROS) is essential for mitochondrial insertion of BNip3, which is an important step in BNip3-induced mitochondrial catastrophe. Our results indicate that BNip3 is a candidate therapeutic target in pathologic conditions in which TNF causes tissue damage.
机译：肿瘤坏死因子（TNF）是一种多效性细胞因子，在许多病理状况下均参与免疫调节，炎症反应和靶细胞死亡。 TNF触发的细胞死亡途径包括caspase-8 / Bid依赖性凋亡途径和caspase依赖性坏死途径（坏死性坏死）。尽管在TNF与TNF受体（TNFR）结合并随后将Bid / Bax / Bik插入线粒体外膜后激活的信号传导途径是众所周知的，但其他细胞死亡途径和参与的信号传导分子仍有待阐明。 BNip3是一种致死蛋白，是仅BH3的Bcl-2家族的成员。当异位过表达或由缺氧诱导时，BNip3会通过线粒体或非线粒体死亡级联反应诱导各种类型的细胞死亡。在这项使用肺A549肺泡上皮细胞的研究中，我们显示BNip3在TNF的转录和翻译上调，并且其表达水平决定了对TNF诱导的坏死病的敏感性。但是，在这些肺泡肺细胞中，BNip3似乎不参与caspase-8 / Bid依赖性凋亡细胞的死亡。最后，我们证明了活性氧（ROS）的生成对于BNip3的线粒体插入至关重要，这是BNip3诱导的线粒体灾难的重要一步。我们的结果表明BNip3是TNF导致组织损伤的病理状况的候选治疗靶标。

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