title: How Trypanosoma cruzi deals with oxidative stress: Antioxidant defence and DNA repair pathways.
abstract: 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.
authors.affiliation: Fundação Oswaldo Cruz, Centro de Desenvolvimento Tecnológico em Saúde (CDTS), Rio de Janeiro, Brazil.
authors.forename: Alice
authors.initials: A
authors.lastname: Machado-Silva
authors.affiliation: Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Bioquímica e Imunologia, Belo Horizonte, Brazil.
authors.forename: Paula Gonçalves
authors.initials: PG
authors.lastname: Cerqueira
authors.affiliation: Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Bioquímica e Imunologia, Belo Horizonte, Brazil.
authors.forename: Viviane
authors.initials: V
authors.lastname: Grazielle-Silva
authors.affiliation: Universidade Estadual de Campinas, Instituto de Biologia, Departamento de Bioquímica e Biologia Tecidual, São Paulo, Brazil.
authors.forename: Fernanda Ramos
authors.initials: FR
authors.lastname: Gadelha
authors.affiliation: Universidade Estadual de Campinas, Instituto de Biologia, Departamento de Bioquímica e Biologia Tecidual, São Paulo, Brazil.
authors.forename: Eduardo de Figueiredo
authors.initials: Ede F
authors.lastname: Peloso
authors.affiliation: Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Bioquímica e Imunologia, Belo Horizonte, Brazil.
authors.forename: Santuza Maria Ribeiro
authors.initials: SM
authors.lastname: Teixeira
authors.affiliation: Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas, Departamento de Bioquímica e Imunologia, Belo Horizonte, Brazil. Electronic address: crmachad@icb.ufmg.br.
authors.forename: Carlos Renato
authors.initials: CR
authors.lastname: Machado
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D014355:Chagas Disease / Q000469:parasitology / Q000628:therapy; D004249:DNA Damage / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics*; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014349:Trypanosoma cruzi / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species
keywords: DNA repair; Genetic diversity; Oxidative stress; Trypanosoma cruzi