首页    期刊浏览 2024年11月30日 星期六
登录注册

文章基本信息

  • 标题:PTEN inhibitor bpV(HOpic) confers protection against ionizing radiation
  • 本地全文:下载
  • 作者:Ankit Chauhan ; Dhananjay Kumar Sah ; Neeraj Kumari
  • 期刊名称:Scientific Reports
  • 电子版ISSN:2045-2322
  • 出版年度:2021
  • 卷号:11
  • 期号:1
  • 页码:1720
  • DOI:10.1038/s41598-020-80754-8
  • 出版社:Springer Nature
  • 摘要:Abstract Exposure to Ionizing radiation (IR) poses a severe threat to human health. Therefore, there is an urgent need to develop potent and safe radioprotective agents for radio-nuclear emergencies. Phosphatidylinositol-3-kinase (PI3K) mediates its cytoprotective signaling against IR by phosphorylating membrane phospholipids to phosphatidylinositol 3,4,5 triphosphate, PIP3, that serve as a docking site for AKT. Phosphatase and Tensin Homolog on chromosome 10 (PTEN) antagonizes PI3K activity by dephosphorylating PIP3, thus suppressing PI3K/AKT signaling that could prevent IR induced cytotoxicity. The current study was undertaken to investigate the radioprotective potential of PTEN inhibitor (PTENi), bpV(HOpic). The cell cytotoxicity, proliferation index, and clonogenic survival assays were performed for assessing the radioprotective potential of bpV(HOpic). A safe dose of bpV(HOpic) was shown to be radioprotective in three radiosensitive tissue origin cells. Further, bpV(HOpic) significantly reduced the IR-induced apoptosis and associated pro-death signaling. A faster and better DNA repair kinetics was also observed in bpV(HOpic) pretreated cells exposed to IR. Additionally, bpV(HOpic) decreased the IR-induced oxidative stress and significantly enhanced the antioxidant defense mechanism in cells. The radioprotective effect of bpV(HOpic) was found to be AKT dependant and primarily regulated by the enhanced glycolysis and associated signaling. Furthermore, this in-vitro observation was verified in-vivo, where administration of bpV(HOpic) in C57BL/6 mice resulted in AKT activation and conferred survival advantage against IR-induced mortality. These results imply that bpV(HOpic) ameliorates IR-induced oxidative stress and cell death by inducing AKT signaling mediated antioxidant defense system and DNA repair pathways, thus strengthening its potential to be used as a radiation countermeasure.
国家哲学社会科学文献中心版权所有