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How Trypanosoma cruzi deals with oxidative stress: Antioxidant defence and DNA repair pathways.
Mutation Research/Reviews in Mutation Research ( IF 6.4 ) Pub Date : 2016-04-03 , DOI: 10.1016/j.mrrev.2015.12.003
Alice Machado-Silva 1 , Paula Gonçalves Cerqueira 2 , Viviane Grazielle-Silva 2 , Fernanda Ramos Gadelha 3 , Eduardo de Figueiredo Peloso 3 , Santuza Maria Ribeiro Teixeira 2 , Carlos Renato Machado 2
Affiliation  

Trypanosoma cruzi, the causative agent of Chagas disease, is an obligatory intracellular parasite with a digenetic life cycle. Due to the variety of host environments, it faces several sources of oxidative stress. In addition to reactive oxygen species (ROS) produced by its own metabolism, T. cruzi must deal with high ROS levels generated as part of the host's immune responses. Hence, the conclusion that T. cruzi has limited ability to deal with ROS (based on the lack of a few enzymes involved with oxidative stress responses) seems somewhat paradoxical. Actually, to withstand such variable sources of oxidative stress, T. cruzi has developed complex defence mechanisms. This includes ROS detoxification pathways that are distinct from the ones in the mammalian host, DNA repair pathways and specialized polymerases, which not only protect its genome from the resulting oxidative damage but also contribute to the generation of genetic diversity within the parasite population. Recent studies on T. cruzi's DNA repair pathways as mismatch repair (MMR) and GO system suggested that, besides a role associated with DNA repair, some proteins of these pathways may also be involved in signalling oxidative damage. Recent data also suggested that an oxidative environment might be beneficial for parasite survival within the host cell as it contributes to iron mobilization from the host's intracellular storages. Besides contributing to the understanding of basic aspects of T. cruzi biology, these studies are highly relevant since oxidative stress pathways are part of the poorly understood mechanisms behind the mode of action of drugs currently used against this parasite. By unveiling new peculiar aspects of T. cruzi biology, emerging data on DNA repair pathways and other antioxidant defences from this parasite have revealed potential new targets for a much needed boost in drug development efforts towards a better treatment for Chagas disease.

中文翻译:

克氏锥虫如何应对氧化应激:抗氧化防御和DNA修复途径。

恰加斯氏锥虫是恰加斯氏病的病原体,是一种具有双基因生命周期的强制性细胞内寄生虫。由于宿主环境的多样性,它面临多种氧化应激源。除了自身代谢产生的活性氧(ROS)以外,克鲁氏梭菌还必须处理作为宿主免疫反应一部分而产生的高ROS水平。因此,克氏锥虫处理ROS的能力有限的结论(由于缺乏与氧化应激反应有关的几种酶)似乎有些自相矛盾。实际上,为了抵御这种可变的氧化应激源,克鲁氏锥虫已开发出复杂的防御机制。这包括与哺乳动物宿主不同的ROS解毒途径,DNA修复途径和专门的聚合酶,不仅保护其基因组免受氧化损伤,而且有助于寄生虫种群内遗传多样性的产生。对克鲁斯氏菌的DNA修复途径失配修复(MMR)和GO系统的最新研究表明,除了与DNA修复相关的作用外,这些途径中的某些蛋白质也可能参与了氧化损伤的信号传导。最近的数据还表明,氧化环境可能有助于宿主细胞内的寄生虫存活,因为它有助于从宿主细胞内存储物中动员铁。除了有助于了解克氏锥虫生物学的基本方面,这些研究是高度相关的,因为氧化应激途径是目前针对这种寄生虫的药物作用方式背后鲜为人知的机制的一部分。通过揭示克鲁维氏锥虫生物学的新奇特征,有关该寄生虫的DNA修复途径和其他抗氧化剂防御的新兴数据揭示了潜在的新靶标,这些靶标是迫切需要促进药物开发工作以更好地治疗南美锥虫病的药物。
更新日期:2019-11-01
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