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首页> 外文学位 >Targeting 8-oxoguanine DNA glycosylase to mitochondria enhances mitochondrial DNA repair and cellular resistance to oxidative stress.
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Targeting 8-oxoguanine DNA glycosylase to mitochondria enhances mitochondrial DNA repair and cellular resistance to oxidative stress.

机译：将8-氧鸟嘌呤DNA糖基化酶靶向线粒体可增强线粒体DNA修复和细胞对氧化应激的抵抗力。

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摘要

Oxidative damage to mitochondrial DNA has been implicated as a causative factor in many disease processes and in aging. Because different cell types have demonstrated varying abilities for repairing this damage, we have investigated the effects of enhancing mtDNA repair in two cell types that are relatively deficient in repair. Specifically, the enzyme that repairs the mutagenic lesion 8-oxoguanine in the nucleus, called 8-oxoguanine DNA glycosylase (OGG), was targeted to mitochondria. A vector containing this gene fused to a mitochondrial transport sequence was used to transfect human cell lines. Localization of the protein and enzyme activity were analyzed. Then mtDNA repair was evaluated. Finally, the effect of changes in mtDNA repair was studied with several viability assays. Initial studies employed an isolate of HeLa cells with inefficient mtDNA repair, and subsequent experiments were done with Cockayne syndrome A fibroblasts. We hypothesized that increasing levels of OGG, a critical DNA repair enzyme, in mitochondria could alter the ability of the cell to repair oxidative damage to mtDNA. As a result, cell sensitivity to oxidative stress might also be changed. Targeting OGG exclusively to mitochondria in HeLa cells resulted in more efficient mtDNA repair and better cellular resistance to oxidative insult. Cockayne Syndrome A fibroblasts were protected by additional mitochondrial OGG as well. Therefore, targeting of DNA repair enzymes to mitochondria appears to have potential as a therapeutic procedure for combating the accumulation of mtDNA damage observed with aging and other degenerative conditions.
机译：线粒体DNA的氧化损伤被认为是许多疾病过程和衰老的致病因素。由于不同的细胞类型已显示出修复这种损伤的能力各不相同，因此我们研究了在修复相对不足的两种细胞类型中增强mtDNA修复的效果。具体而言，修复细胞核中诱变病变的8-氧鸟嘌呤的酶称为8-氧鸟嘌呤DNA糖基化酶（OGG），靶向线粒体。含有与线粒体转运序列融合的该基因的载体被用于转染人细胞系。分析蛋白质的定位和酶活性。然后评估mtDNA修复。最后，通过几种生存力分析研究了mtDNA修复变化的影响。最初的研究使用了分离的mtDNA修复效率低下的HeLa细胞，随后对Cockayne综合征A成纤维细胞进行了实验。我们假设线粒体中OGG（一种重要的DNA修复酶）水平升高可能会改变细胞修复mtDNA氧化损伤的能力。结果，细胞对氧化应激的敏感性也可能改变。将OGG专门靶向HeLa细胞中的线粒体可导致更有效的mtDNA修复和更好的细胞抗氧化性。 Cockayne综合征A成纤维细胞也受到其他线粒体OGG的保护。因此，将DNA修复酶靶向线粒体似乎具有作为治疗程序的潜力，该程序可用于对抗因老化和其他退化条件而观察到的mtDNA损伤累积。

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  • 作者

    Dobson, Allison Williams.;

  • 作者单位

    University of South Alabama.;

  • 授予单位 University of South Alabama.;
  • 学科 Biology Molecular.; Chemistry Biochemistry.
  • 学位 Ph.D.
  • 年度 2001
  • 页码 93 p.
  • 总页数 93
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;生物化学;
  • 关键词

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