首页> 外文期刊>Journal of biochemical and molecular toxicology >Generation of an oxidative stress precedes caspase activation during 7beta-hydroxycholesterol-induced apoptosis in U937 cells.
【24h】

Generation of an oxidative stress precedes caspase activation during 7beta-hydroxycholesterol-induced apoptosis in U937 cells.

机译:在7β-羟基胆固醇诱导的U937细胞凋亡中,氧化应激的产生先于caspase活化。

获取原文
获取原文并翻译 | 示例
           

摘要

The oxysterol 7beta-hydroxycholesterol (7beta-OH) has been shown to induce apoptosis in a number of cell lines. Though not fully elucidated, the mechanism through which this oxysterol induces cell death is thought to involve the generation of an oxidative stress leading to perturbation of the mitochondrion and release of cytochrome c into the cytosol. Cytochrome c together with Apaf-1 causes activation of the initiator caspase, caspase-9, which in turn activates caspase-3 ultimately leading to the degradation of poly(ADP-ribose) polymerase (PARP). The objective of the present study was to investigate the signalling pathway in 7beta-OH-induced apoptosis in U937 cells, a human monocytic blood cell line known to undergo apoptosis upon treatment with 7beta-OH, over a time course of 48 h. Apoptosis was evident after 24 h incubation. Glutathione levels were decreased after 6 h and this was coupled with an increase in SOD activity. Through western blot analysis we examined expression of caspase-3, -8, and -9 and cleavage of the caspase-3 substrate PARP. The sequence proceeded with activation of caspase-9 after 9 h, caspase-3 at the 12 h timepoint, and cleavage of PARP after 24 h treatment with 7beta-OH. Caspase-8 did not appear to play a major role in this particular apoptotic pathway.
机译:氧固醇7β-羟基胆固醇(7beta-OH)已显示在许多细胞系中诱导凋亡。尽管尚未完全阐明,但该氧固醇诱导细胞死亡的机制被认为涉及氧化应激的产生,导致线粒体的扰动和细胞色素c释放到胞质溶胶中。细胞色素c与Apaf-1一起引起启动子胱天蛋白酶caspase-9的激活,而后者又激活caspase-3,最终导致聚ADP-核糖聚合酶(PARP)降解。本研究的目的是研究U937细胞中7β-OH诱导的细胞凋亡的信号通路,U937细胞是已知的人单核细胞系,在经过7h-OH处理后会在48小时内发生凋亡。孵育24小时后细胞凋亡明显。 6小时后谷胱甘肽水平降低,这与SOD活性增加有关。通过蛋白质印迹分析,我们检查了caspase-3,-8和-9的表达以及caspase-3底物PARP的切割。该序列在9小时后激活caspase-9,在12小时时激活caspase-3,并在用7β-OH处理24小时后裂解PARP。 Caspase-8在这一特定的凋亡途径中似乎没有发挥主要作用。

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