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Protective effects of polyphenolic compounds on cobalt chloride- and hydrogen peroxide-induced cytotoxicity in PC12 cells .

机译:多酚类化合物对氯化钴和过氧化氢诱导的PC12细胞毒性的保护作用。

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摘要

Elevated levels of reactive oxygen species (ROS) have been implicated in the pathogenesis of many diseases. Recent studies suggest beneficial effects, and increased overall health, are associated with consumption of foods rich in polyphenols such as fruits, wines and teas. Further, studies demonstrate that polyphenols, specifically epigallocatechin gallate (EGCG) act as potent scavengers, metal chelators and regulators of survival genes, and may promote survival in oxidatively stressed cells by reducing intracellular levels of ROS and inhibiting key steps in the apoptotic pathway. In light of this research, polyphenols have been proven successful in treating and delaying the onset of neurodegenerative disorders such as Parkinson's disease. In an effort to better understand beneficial properties of polyphenols in oxidative stress conditions, the aim of this study was to screen 12 polyphenols for their ability to increase viability of PC12 cells stressed via cobalt chloride (CoCl 2) or hydrogen peroxide (H2O2). Further, to better understand protective mechanisms, the neuroprotective effects of polyphenols showing increased viability under stressed conditions were investigated in PC12 cells subjected to H2O2-induced apoptosis.;Cell viability data presented here demonstrates that methyl gallate (MG) was the only polyphenol to exert protective effects under H2O 2 stressed conditions. Although EGCG did not demonstrate the ability to increase survival of stressed cells, EGCG, MG and gallic acid (GA) proved beneficial in reducing intracellular levels of CoCl2-derived ROS. Quantitation of apoptosis and mitochondrial membrane potential shows that MG pre-treatment prevents mitochondrial depolarization however does not inhibit apoptosis. Analysis of DNA degradation and caspase activation demonstrate that MG inhibits activation of caspase 9 and has a partial inhibitory effect on DNA degradation, suggesting involvement of the death receptor-mediated pathway. These findings suggest that MG may possess beneficial properties against ROS associated diseases and oxidative stress-induced apoptosis.
机译:活性氧(ROS)水平升高与许多疾病的发病机理有关。最近的研究表明,食用富含多酚的食物(例如水果,葡萄酒和茶)会带来有益的影响并增强整体健康状况。此外,研究表明,多酚,特别是表没食子儿茶素没食子酸酯(EGCG)充当有效的清除剂,金属螯合剂和存活基因的调节剂,并可能通过降低细胞内ROS水平并抑制凋亡途径的关键步骤来促进氧化应激细胞的存活。根据这项研究,已证明多酚可成功治疗和延缓神经退行性疾病(如帕金森氏病)的发作。为了更好地了解多酚在氧化应激条件下的有益特性,本研究的目的是筛选12种多酚提高通过氯化钴(CoCl 2)或过氧化氢(H2O2)胁迫的PC12细胞活力的能力。此外,为了更好地了解保护机制,在受H2O2诱导的PC12细胞中研究了多酚在压力条件下显示出增强的生存能力的神经保护作用。;此处提供的细胞生存力数据表明,没食子酸甲酯(MG)是唯一发挥作用的多酚H2O 2胁迫条件下的保护作用。尽管EGCG并未显示出增加应激细胞存活的能力,但EGCG,MG和没食子酸(GA)被证明有助于降低CoCl2衍生的ROS的细胞内水平。凋亡和线粒体膜电位的定量显示,MG预处理可以防止线粒体去极化,但是不能抑制凋亡。 DNA降解和caspase激活的分析表明,MG抑制caspase 9的激活,并且对DNA降解具有部分抑制作用,表明参与了死亡受体介导的途径。这些发现表明,MG可能具有抵抗ROS相关疾病和氧化应激诱导的细胞凋亡的有益特性。

著录项

  • 作者

    Crispo, James A.G.;

  • 作者单位

    Laurentian University (Canada).;

  • 授予单位 Laurentian University (Canada).;
  • 学科 Biology Cell.
  • 学位 M.Sc.
  • 年度 2010
  • 页码 104 p.
  • 总页数 104
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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