• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of dermatological science >Telomeric DNA induces p53-dependent reactive oxygen species and protects against oxidative damage
【24h】

Telomeric DNA induces p53-dependent reactive oxygen species and protects against oxidative damage

机译：端粒DNA诱导p53依赖的活性氧，并保护其免受氧化损伤

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

Background: Reactive oxygen species (ROS) are generated by cellular metabolism as well as by exogenous agents. While ROS can promote cellular senescence, they can also act as signaling molecules for processes that do not lead to senescence. Telomere homolog oligonucleotides (T-oligos) induce adaptive DNA damage responses including increased DNA repair capacity and these effects are mediated, at least in part, through p53. Objective: Studies were undertaken to determine whether such p53-mediated protective responses include enhanced antioxidant defenses. Methods: Normal human fibroblasts as well as R2F fibroblasts expressing wild type or dominant negative p53 were treated with an 11-base T-oligo, a complementary control oligo or diluents alone and then examined by western blot analysis, immunofluorescence microscopy and various biochemical assays. Results: We now report that T-oligo increases the level of the antioxidant enzymes superoxide dismutase 1 and 2 and protects cells from oxidative damage; and that telomere-based γH2AX (DNA damage) foci that form in response to T-oligos contain phosphorylated ATM and Chk2, proteins known to activate p53 and to mediate cell cycle arrest in response to oxidative stress. Further, T-oligo increases cellular ROS levels via a p53-dependent pathway, and these increases are abrogated by the NAD(P)H oxidase inhibitor diphenyliodonium chloride. Conclusion: These results suggest the existence of innate telomere-based protective responses that act to reduce oxidative damage to cells. T-oligo treatment induces the same responses and offers a new model for studying intracellular ROS signaling and the relationships between DNA damage, ROS, oxidative stress, and cellular defense mechanisms.
机译：背景：活性氧（ROS）是由细胞代谢以及外源性物质产生的。尽管ROS可以促进细胞衰老，但它们也可以充当不导致衰老的过程的信号分子。端粒同源寡核苷酸（T-oligos）诱导适应性DNA损伤反应，包括增加的DNA修复能力，这些作用至少部分通过p53介导。目的：进行了研究以确定这种p53介导的保护反应是否包括增强的抗氧化剂防御能力。方法：正常人成纤维细胞以及表达野生型或显性负性p53的R2F成纤维细胞分别用11个碱基的T-寡核苷酸，互补性对照寡核苷酸或稀释剂处理，然后通过蛋白质印迹分析，免疫荧光显微镜和各种生化分析进行检查。结果：我们现在报道，T-寡核苷酸可提高抗氧化酶超氧化物歧化酶1和2的水平，并保护细胞免受氧化损伤;响应T寡核苷酸而形成的基于端粒的γH2AX（DNA损伤）灶包含磷酸化的ATM和Chk2，这两种蛋白已知可激活p53并在氧化应激中介导细胞周期停滞。此外，T-寡核苷酸通过p53依赖性途径增加细胞ROS水平，而这些增加被NAD（P）H氧化酶抑制剂二苯基碘化鎓氯化物所消除。结论：这些结果表明存在先天的基于端粒的保护性反应，可减少细胞的氧化损伤。 T-寡核苷酸治疗诱导相同的反应，并为研究细胞内ROS信号以及DNA损伤，ROS，氧化应激和细胞防御机制之间的关系提供了新模型。

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