How Trypanosoma cruzi deals with oxidative stress: Antioxidant defence and DNA repair pathways

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• 作者：Alice Machado-Silva^a ; Paula Gonç ; alves Cerqueira^b ; Viviane Grazielle-Silva^b ; Fernanda Ramos Gadelha^c ; Eduardo de Figueiredo Peloso^c ; Santuza Maria Ribeiro Teixeira^b ; Carlos Renato Machado^b ; ^{crmachad@icb.ufmg.br" class="auth_mail" title="E-mail the corresponding author}
• 关键词：ROS ; reactive oxygen species ; O2&minus ; superoxide anions ; H2O2 ; hydrogen peroxide ; SOD ; superoxide dismutase ; OH ; hydroxyl radicals ; NO ; nitric oxide ; NOS ; nitric oxide synthase ; iNOS ; inducible nitric oxide synthase ; P5C ; D1-pyrroline-5-carboxylate ; ROI ; reactive oxygen intermediates ; RNI ; reactive nitrogen intermediates ; proPO ; prophenoloxidase ; PO ; phenoloxidase ; TAO ; alternative oxidase ; T(SH)2 ; trypanothione ; GSH ; glutathione ; TR ; trypanothione reductase ; TcMPx ; mitochondrial tryparedoxin
• 刊名：Mutation Research/Reviews in Mutation Research
• 出版年：2016
• 出版时间：January-March 2016
• 年：2016
• 卷：767
• 期：Complete
• 页码：8-22
• 全文大小：891 K

文摘

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.