Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/13187
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dc.contributor.authorFerrão, Patrícia Mello
dc.contributor.authorLevy, Claudia Masini d'Avila
dc.contributor.authorAraujo-Jorge, Tania C.
dc.contributor.authorDegrave, Wim Maurits
dc.contributor.authorGonçalves, Antônio da Silva
dc.contributor.authorGarzoni, Luciana Ribeiro
dc.contributor.authorLima, Ana Paula
dc.contributor.authorFeige, Jean Jacques
dc.contributor.authorBailly, Sabine
dc.contributor.authorLima, Leila Mendonça
dc.contributor.authorWaghabi, Mariana Caldas
dc.date.accessioned2016-03-16T13:32:04Z
dc.date.available2016-03-16T13:32:04Z
dc.date.issued2015
dc.identifier.citationFERRÃO, Patrícia Mello; et al. Cruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion. Plos One, v.10, n.5, e0124832, 15p, May 2015.
dc.identifier.issn1932-6203
dc.identifier.urihttps://www.arca.fiocruz.br/handle/icict/13187
dc.language.isoeng
dc.publisherPublic Library of Science
dc.rightsopen access
dc.titleCruzipain Activates Latent TGF-β from Host Cells during T. cruzi Invasion
dc.typeArticle
dc.identifier.doi10.1371/journal.pone.0124832
dc.description.abstractenSeveral studies indicate that the activity of cruzipain, the main lysosomal cysteine peptidase of Trypanosoma cruzi, contributes to parasite infectivity. In addition, the parasitic invasion process of mammalian host cells is described to be dependent on the activation of the host TGF-β signaling pathway by T. cruzi. Here, we tested the hypothesis that cruzipain could be an important activator of latent TGF-β and thereby trigger TGF-β-mediated events crucial for the development of Chagas disease. We found that live epimastigotes of T. cruzi, parasite lysates and purified cruzipain were able to activate latent TGF-β in vitro. This activation could be inhibited by the cysteine peptidase inhibitor Z-Phe-Ala-FMK. Moreover, transfected parasites overexpressing chagasin, a potent endogenous cruzipain inhibitor, prevented latent TGF-β activation. We also observed that T. cruzi invasion, as well as parasite intracellular growth, were inhibited by the administration of Z-Phe-Ala-FMK or anti-TGF-β neutralizing antibody to Vero cell cultures. We further demonstrated that addition of purified cruzipain enhanced the invasive activity of trypomastigotes and that this effect could be completely inhibited by addition of a neutralizing anti-TGF-β antibody. Taken together, these results demonstrate that the activities of cruzipain and TGF-β in the process of cell invasion are functionally linked. Our data suggest that cruzipain inhibition is an interesting chemotherapeutic approach for Chagas disease not only because of its trypanocidal activity, but also due to the inhibitory effect on TGF-β activation.
dc.creator.affilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil.
dc.creator.affilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil.
dc.creator.affilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ, Brasil.
dc.creator.affilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
dc.creator.affilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia de Infecções Virais. Rio de Janeiro, RJ, Brasil.
dc.creator.affilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Investigação Cardiovascular. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Programa Integrado de Doença de Chagas. Rio de Janeiro, RJ, Brasil.
dc.creator.affilliationUniversidade Federal do Rio de Janeiro. Instituto de Biofisica Carlos Chagas Filho. Laboratório de Bioquímica e Biologia Molecular de Peptidases. Rio de Janeiro, RJ, Brasil.
dc.creator.affilliationINSERM, Unité 1036, Grenoble, F-38054, France / Université Grenoble-Alpes—Grenoble, F-38041, France, CEA, DSV,iRTSV, Laboratory of Biology of Cancer and Infection, Grenoble, F-38054, France.
dc.creator.affilliationINSERM, Unité 1036, Grenoble, F-38054, France / Université Grenoble-Alpes—Grenoble, F-38041, France, CEA, DSV,iRTSV, Laboratory of Biology of Cancer and Infection, Grenoble, F-38054, France.
dc.creator.affilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil.
dc.creator.affilliationFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Programa Integrado de Doença de Chagas. Rio de Janeiro, RJ, Brasil.
dc.subject.enTrypanosoma cruzi
dc.subject.enChagas Disease
dc.subject.enTGF-β
dc.subject.enHost Cells
dc.subject.enCruzipain
dc.subject.decsTrypanosoma cruzi
dc.subject.decsDoença de Chagas
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