Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model

Detalhes bibliográficos
Autor(a) principal: Sangenito, Leandro S
Data de Publicação: 2014
Outros Autores: Menna-Barreto, Rubem F. S., d`Avila-Levy, Claudia M., Santos, André L. S, Branquinha, Marta H
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/10060
Resumo: Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil.
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spelling Sangenito, Leandro SMenna-Barreto, Rubem F. S.d`Avila-Levy, Claudia M.Santos, André L. SBranquinha, Marta H2015-04-17T17:04:29Z2015-04-17T17:04:29Z2014SANGENITO, Leandro s. et al. Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model. PLoS ONE, v.9, n.12, 25p, 2014.https://www.arca.fiocruz.br/handle/icict/1006010.1371/journal.pone.0113957engPlos OneDoença de ChagasHIVTripanosoma cruziParasitosChagas diseaseHIVTripanosoma cruziParasitesMicrobiologiaSaúde PúblicaDecoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Modelinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, BrasilFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Química. Programa de Pós-Graduação em Bioquímica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil.Background: Aspartic peptidase inhibitors have shown antimicrobial action against distinct microorganisms. Due to an increase in the occurrence of Chagas’ disease/AIDS co-infection, we decided to explore the effects of HIV aspartic peptidase inhibitors (HIV-PIs) on Trypanosoma cruzi, the etiologic agent of Chagas’ disease. Methodology and Principal Findings: HIV-PIs presented an anti-proliferative action on epimastigotes of T. cruzi clone Dm28c, with IC50 values ranging from 0.6 to 14 mM. The most effective inhibitors, ritonavir, lopinavir and nelfinavir, also had an anti-proliferative effect against different phylogenetic T. cruzi strains. The HIVPIs induced some morphological alterations in clone Dm28c epimastigotes, as reduced cell size and swollen of the cellular body. Transmission electron microscopy revealed that the flagellar membrane, mitochondrion and reservosomes are the main targets of HIV-PIs in T. cruzi epimastigotes. Curiously, an increase in the epimastigote-into-trypomastigote differentiation process of clone Dm28c was observed, with many of these parasites presenting morphological alterations including the detachment of flagellum from the cell body. The pretreatment with the most effective HIV-PIs drastically reduced the interaction process between epimastigotes and the invertebrate vector Rhodnius prolixus. It was also noted that HIV-PIs induced an increase in the expression of gp63-like and calpain-related molecules, and decreased the cruzipain expression in epimastigotes as judged by flow cytometry and immunoblotting assays. The hydrolysis of a cathepsin D fluorogenic substrate was inhibited by all HIV-PIs in a dose-dependent manner, showing that the aspartic peptidase could be a possible target to these drugs. Additionally, we verified that ritonavir, lopinavir and nelfinavir reduced drastically the viability of clone Dm28c trypomastigotes, causing many morphological damages. Conclusions and Significance: The results contribute to understand the possible role of aspartic peptidases in T. cruzi physiology, adding new in vitro insights into the possibility of exploiting the use of HIV-PIs in the clinically relevant forms of the parasite.info:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txttext/plain1914https://www.arca.fiocruz.br/bitstream/icict/10060/1/license.txt7d48279ffeed55da8dfe2f8e81f3b81fMD51ORIGINALrubem_mennabarretoetal2_IOC_2014.pdfapplication/pdf2175139https://www.arca.fiocruz.br/bitstream/icict/10060/2/rubem_mennabarretoetal2_IOC_2014.pdf6a0196b654df473c1f1556cd07cf8120MD52TEXTrubem_mennabarretoetal2_IOC_2014.pdf.txtrubem_mennabarretoetal2_IOC_2014.pdf.txtExtracted texttext/plain70048https://www.arca.fiocruz.br/bitstream/icict/10060/3/rubem_mennabarretoetal2_IOC_2014.pdf.txtacf7778c793398625e5ba58e69d234e6MD53icict/100602022-06-24 13:10:48.876oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T16:10:48Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model
title Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model
spellingShingle Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model
Sangenito, Leandro S
Doença de Chagas
HIV
Tripanosoma cruzi
Parasitos
Chagas disease
HIV
Tripanosoma cruzi
Parasites
Microbiologia
Saúde Pública
title_short Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model
title_full Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model
title_fullStr Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model
title_full_unstemmed Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model
title_sort Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model
author Sangenito, Leandro S
author_facet Sangenito, Leandro S
Menna-Barreto, Rubem F. S.
d`Avila-Levy, Claudia M.
Santos, André L. S
Branquinha, Marta H
author_role author
author2 Menna-Barreto, Rubem F. S.
d`Avila-Levy, Claudia M.
Santos, André L. S
Branquinha, Marta H
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Sangenito, Leandro S
Menna-Barreto, Rubem F. S.
d`Avila-Levy, Claudia M.
Santos, André L. S
Branquinha, Marta H
dc.subject.other.pt_BR.fl_str_mv Doença de Chagas
HIV
Tripanosoma cruzi
Parasitos
topic Doença de Chagas
HIV
Tripanosoma cruzi
Parasitos
Chagas disease
HIV
Tripanosoma cruzi
Parasites
Microbiologia
Saúde Pública
dc.subject.en.pt_BR.fl_str_mv Chagas disease
HIV
Tripanosoma cruzi
Parasites
dc.subject.decs.pt_BR.fl_str_mv Microbiologia
Saúde Pública
description Universidade Federal do Rio de Janeiro (UFRJ). Instituto de Microbiologia Paulo de Góes (IMPG). Departamento de Microbiologia Geral. Laboratório de Investigação de Peptidases. Rio de Janeiro, RJ, Brasil.
publishDate 2014
dc.date.issued.fl_str_mv 2014
dc.date.accessioned.fl_str_mv 2015-04-17T17:04:29Z
dc.date.available.fl_str_mv 2015-04-17T17:04:29Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.citation.fl_str_mv SANGENITO, Leandro s. et al. Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model. PLoS ONE, v.9, n.12, 25p, 2014.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/10060
dc.identifier.doi.pt_BR.fl_str_mv 10.1371/journal.pone.0113957
identifier_str_mv SANGENITO, Leandro s. et al. Decoding the Anti-Trypanosoma cruzi Action of HIV Peptidase Inhibitors Using Epimastigotes as a Model. PLoS ONE, v.9, n.12, 25p, 2014.
10.1371/journal.pone.0113957
url https://www.arca.fiocruz.br/handle/icict/10060
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
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dc.publisher.none.fl_str_mv Plos One
publisher.none.fl_str_mv Plos One
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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