首页> 外文期刊>RSC Advances >His18 promotes reactive oxidative stress production in copper-ion mediated human islet amyloid polypeptide aggregation
【24h】

His18 promotes reactive oxidative stress production in copper-ion mediated human islet amyloid polypeptide aggregation

机译:HIS18促进铜离子介导人胰岛淀粉样蛋白多肽聚集体中的反应性氧化应激产生

获取原文
           

摘要

Copper ions play a critical role in human islet amyloid polypeptide (hIAPP) aggregation, which has been found in more than 90% of patients with type-2 diabetes (T2D). The role of Cu( II ) in the cell cytotoxicity with hIAPP has been explored in two aspects: inhibiting the formation of fibrillar structures and stimulating the generation of reactive oxygen species (ROS). In this work, we carried out spectroscopic studies of Cu( II ) interacting with several hIAPP fragments and their variants as well. Electron paramagnetic resonance (EPR) measurements and Amplex Red analysis showed that the amount of H _(2) O _(2) generated in hIAPP(11-28) solution co-incubated with Cu( II ) was remarkably more than hIAPP(1-11) and hIAPP(28-37). Furthermore, the H _(2) O _(2) level was seriously reduced when His18 of hIAPP(11-28) was replaced by Arg(R) or Ser(S), indicating that His18 is the key residue of Cu( II ) binding to hIAPP(11-28) to promote H _(2) O _(2) generation. This is likely because the donation of electrons from the peptide to Cu( II ) ions would result in the formation of the redox-active complexes, which could stimulate the formation of H _(2) O _(2) . Overall, this study provides further insight into the molecular mechanism of Cu( II ) induced ROS generation.
机译:铜离子在人胰岛淀粉样蛋白多肽(HIAPP)聚集中发挥着关键作用,这些聚集在超过90%的糖尿病患者(T2D)中被发现。在两个方面探讨了Cu(II)与HIAPP细胞细胞毒性的作用:抑制成纤维结构的形成并刺激反应性氧(ROS)的产生。在这项工作中,我们也对Cu(II)与几种HiaPP片段及其变体相互作用的光谱研究。电子顺磁共振(EPR)测量和AMPLEX红色分析表明,与Cu(II)共孵育的HIAPP(11-28)溶液中产生的H _(2)O _(2)的量显着大于HIAPP(1 -11)和HIAPP(28-37)。此外,当HIAPP(11-28)的HIAPP(11-28)被Arg(R)或Ser(S)取代时,H _(2)O _(2)水平严重降低,表明HIS18是Cu的关键残留物(II )与HIAPP(11-28)结合,以促进H _(2)O _(2)代。这可能是因为从肽捐赠给Cu(II)离子的电子将导致氧化还原活性配合物的形成,这可以刺激H _(2)O _(2)的形成。总体而言,本研究进一步了解Cu(II)诱导的ROS产生的分子机制。

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