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Proliferation and differentiation of Trypanosoma cruzi inside its vector have a new trigger: redox status

Nogueira NP1, Saraiva FM1, Sultano PE1, Cunha PR2, Laranja GA1, Justo GA3, Sabino KC3, Coelho MG3, Rossini A4, Atella GC5, Paes MC6. PLoS One. 2015 ;10(2):e0116712.

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1Laboratório de Interação Tripanossomatídeos e Vetores-Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brasil.

2Laboratório de Bioquímica de Lipídeos e Lipoproteínas-Instituto de Bioquímica Médica Leopoldo de Meis (IBqM), Universidade Federal do Rio de Janeiro (UFRJ)-Rio de Janeiro, Brasil.

3Laboratório de Imunologia Aplicada à Bioquímica de Proteínas e Produtos Naturais-Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brasil.

4Laboratório de Toxicologia e Biologia Molecular, Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brasil.

5Instituto Nacional de Ciência e Tecnologia-Entomologia Molecular (INCT-EM)-Rio de Janeiro, Brasil; Laboratório de Bioquímica de Lipídeos e Lipoproteínas-Instituto de Bioquímica Médica Leopoldo de Meis (IBqM), Universidade Federal do Rio de Janeiro (UFRJ)-Rio de Janeiro, Brasil.

6Laboratório de Interação Tripanossomatídeos e Vetores-Departamento de Bioquímica, Instituto de Biologia Roberto Alcantara Gomes (IBRAG), Universidade do Estado do Rio de Janeiro (UERJ), Rio de Janeiro, Brasil; Instituto Nacional de Ciência e Tecnologia-Entomologia Molecular (INCT-EM)-Rio de Janeiro, Brasil.

 

Abstract

Trypanosoma cruzi proliferate and differentiate inside different compartments of triatomines gut that is the first environment encountered by T. cruzi. Due to its complex life cycle, the parasite is constantly exposed to reactive oxygen species (ROS). We tested the influence of the pro-oxidant molecules H2O2 and the superoxide generator, Paraquat, as well as, metabolism products of the vector, with distinct redox status, in the proliferation and metacyclogenesis. These molecules are heme, hemozoin and urate. We also tested the antioxidants NAC and GSH. Heme induced the proliferation of epimastigotes and impaired the metacyclogenesis. β-hematin, did not affect epimastigote proliferation but decreased parasite differentiation. Conversely, we show that urate, GSH and NAC dramatically impaired epimastigote proliferation and during metacyclogenesis, NAC and urate induced a significant increment of trypomastigotes and decreased the percentage of epimastigotes. We also quantified the parasite loads in the anterior and posterior midguts and in the rectum of the vector by qPCR. The treatment with the antioxidants increased the parasite loads in all midgut sections analyzed. In vivo, the group of vectors fed with reduced molecules showed an increment of trypomastigotes and decreased epimastigotes when analyzed by differential counting. Heme stimulated proliferation by increasing the cell number in the S and G2/M phases, whereas NAC arrested epimastigotes in G1 phase. NAC greatly increased the percentage of trypomastigotes. Taken together, these data show a shift in the triatomine gut micro environment caused by the redox status may also influence T. cruzi biology inside the vector. In this scenario, oxidants act to turn on epimastigote proliferation while antioxidants seem to switch the cycle towards metacyclogenesis. This is a new insight that defines a key role for redox metabolism in governing the parasitic life cycle.

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Proliferation and differentiation of Trypanosoma cruzi inside its vector have a new trigger: redox status. Global Medical Discovery