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过氧化氢酶的表达会损害克氏锥虫中氧化应激介导的信号传导。

Catalase expression impairs oxidative stress-mediated signalling in Trypanosoma cruzi.

作者信息

Freire Anna Cláudia Guimarães, Alves Ceres Luciana, Goes Grazielle Ribeiro, Resende Bruno Carvalho, Moretti Nilmar Silvio, Nunes Vinícius Santana, Aguiar Pedro Henrique Nascimento, Tahara Erich Birelli, Franco Glória Regina, Macedo Andréa Mara, Pena Sérgio Danilo Junho, Gadelha Fernanda Ramos, Guarneri Alessandra Aparecida, Schenkman Sergio, Vieira Leda Quercia, Machado Carlos Renato

机构信息

Departamento de Bioquímica e Imunologia,Universidade Federal de Minas Gerais,Belo Horizonte, MG,Brazil.

Departamento de Microbiologia,Imunologia e Parasitologia,Escola Paulista de Medicina,Universidade Federal de São Paulo,São Paulo, SP,Brazil.

出版信息

Parasitology. 2017 Sep;144(11):1498-1510. doi: 10.1017/S0031182017001044. Epub 2017 Jun 27.

Abstract

Trypanosoma cruzi is exposed to oxidative stresses during its life cycle, and amongst the strategies employed by this parasite to deal with these situations sits a peculiar trypanothione-dependent antioxidant system. Remarkably, T. cruzi's antioxidant repertoire does not include catalase. In an attempt to shed light on what are the reasons by which this parasite lacks this enzyme, a T. cruzi cell line stably expressing catalase showed an increased resistance to hydrogen peroxide (H2O2) when compared with wild-type cells. Interestingly, preconditioning carried out with low concentrations of H2O2 led untransfected parasites to be as much resistant to this oxidant as cells expressing catalase, but did not induce the same level of increased resistance in the latter ones. Also, presence of catalase decreased trypanothione reductase and increased superoxide dismutase levels in T. cruzi, resulting in higher levels of residual H2O2 after challenge with this oxidant. Although expression of catalase contributed to elevated proliferation rates of T. cruzi in Rhodnius prolixus, it failed to induce a significant increase of parasite virulence in mice. Altogether, these results indicate that the absence of a gene encoding catalase in T. cruzi has played an important role in allowing this parasite to develop a shrill capacity to sense and overcome oxidative stress.

摘要

克氏锥虫在其生命周期中会面临氧化应激,而该寄生虫应对这些情况所采用的策略之一是独特的依赖于三磷酸吡啶核苷酸的抗氧化系统。值得注意的是,克氏锥虫的抗氧化机制中不包括过氧化氢酶。为了弄清楚该寄生虫缺乏这种酶的原因,与野生型细胞相比,稳定表达过氧化氢酶的克氏锥虫细胞系对过氧化氢(H₂O₂)的抗性增强。有趣的是,用低浓度H₂O₂进行预处理会使未转染的寄生虫对这种氧化剂的抗性与表达过氧化氢酶的细胞一样强,但不会在后者中诱导相同程度的抗性增加。此外,过氧化氢酶的存在会降低克氏锥虫中三磷酸吡啶核苷酸还原酶的水平,并增加超氧化物歧化酶的水平,导致在用这种氧化剂攻击后残留的H₂O₂水平更高。尽管过氧化氢酶的表达有助于克氏锥虫在红带锥蝽中增殖率的提高,但它未能在小鼠中诱导寄生虫毒力的显著增加。总之,这些结果表明,克氏锥虫中缺乏编码过氧化氢酶的基因在使该寄生虫发展出敏锐的感知和克服氧化应激的能力方面发挥了重要作用。

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