...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Biochemical Pharmacology >AMPK-mediated GSK3beta inhibition by isoliquiritigenin contributes to protecting mitochondria against iron-catalyzed oxidative stress.
【24h】

AMPK-mediated GSK3beta inhibition by isoliquiritigenin contributes to protecting mitochondria against iron-catalyzed oxidative stress.

机译：异寡糖原蛋白对AMPK介导的GSK3β的抑制作用有助于保护线粒体免受铁催化的氧化应激。

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

Isoliquiritigenin (ILQ), a flavonoid compound originated from Glycyrrhiza species, is known to activate SIRT1. Arachidonic acid (AA) in combination with iron (a catalyst of auto-oxidation) leads cells to produce excess reactive species with a change in mitochondrial permeability transition. In view of the importance of oxidative stress in cell death and inflammation, this study investigated the potential of ILQ to protect cells against the mitochondrial impairment induced by AA+iron and the underlying basis for this cytoprotection. Treatment with ILQ inhibited apoptosis induced by AA+iron, as evidenced by alterations in the levels of the proteins associated with cell viability: ILQ prevented a decrease in Bcl-x(L), and cleavage of poly(ADP-ribose)polymerase and procaspase-3. Moreover, ILQ inhibited the ability of AA+iron to elicit mitochondrial dysfunction. In addition, superoxide generation in mitochondria was attenuated by ILQ treatment. Consistently, ILQ prevented cellular H2O2 production increased by AA+iron, thereby enabling cells to restore GSH content. ILQ treatment enhanced inhibitory phosphorylation of glycogen synthase kinase-3beta (GSK3beta), and prevented a decrease in the GSK3beta phosphorylation elicited by AA+iron, which contributed to protecting cells and mitochondria. GSK3beta phosphorylation by ILQ was preceded by AMP-activated protein kinase (AMPK) activation, which was also responsible for mitochondrial protection, as shown by reversal of its effect in the experiments using a dominant negative mutant of AMPK and compound C. Moreover, the AMPK activation led to GSK3beta phosphorylation. These results demonstrate that ILQ has the ability to protect cells from AA+iron-induced H2O2 production and mitochondrial dysfunction, which is mediated with GSK3beta phosphorylation downstream of AMPK.
机译：异黄酮生成素（ILQ）是一种源自甘草种的类黄酮化合物，可激活SIRT1。花生四烯酸（AA）与铁（自氧化催化剂）结合可导致细胞产生过量的反应性物质，并改变线粒体的通透性。考虑到氧化应激在细胞死亡和炎症中的重要性，本研究调查了ILQ保护细胞免受AA +铁诱导的线粒体损伤的潜力以及这种细胞保护的基础。 ILQ的治疗抑制了AA +铁诱导的细胞凋亡，这一点已通过与细胞活力相关的蛋白质水平的改变得到了证明：ILQ阻止了Bcl-x（L）的减少以及聚（ADP-核糖）聚合酶和procaspase的裂解-3。此外，ILQ抑制AA +铁引起线粒体功能障碍的能力。另外，ILQ处理减弱了线粒体中超氧化物的产生。一致地，ILQ阻止了AA +铁增加的细胞H2O2产生，从而使细胞能够恢复GSH含量。 ILQ处理增强了糖原合酶激酶3beta（GSK3beta）的抑制性磷酸化，并防止了AA +铁引起的GSK3beta磷酸化的降低，这有助于保护细胞和线粒体。 ILQ将GSK3beta磷酸化之前，是AMP激活的蛋白激酶（AMPK）激活，它也负责线粒体的保护，如使用AMPK和化合物C的显性负突变体逆转其作用所显示的那样。激活导致GSK3beta磷酸化。这些结果表明，ILQ具有保护细胞免受AA +铁诱导的H2O2产生和线粒体功能障碍的能力，这是由AMPK下游的GSK3beta磷酸化介导的。

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