Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/15709
Title: Effects of a marine serine protease inhibitor on viability and morphology of Trypanosoma cruzi, the agent of Chagas disease
Authors: Nogueira, Natália Pereira de Almeida
Morgado-Díaz, José Andrés
Menna-Barreto, Rubem Figueiredo Sadok
Paes, Marcia Cristina
López, Raquel Elisa da Silva
Affilliation: Universidade do Estado do Rio de Janeiro. Instituto de e Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação de Tripanosomatídeos e Vetores. Rio de Janeiro, RJ, Brasil.
Instituto Nacional de Câncer. Divisão de Biologia Celular, Pesquisa Básica. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ, Brasil.
Universidade do Estado do Rio de Janeiro. Instituto de e Biologia Roberto Alcântara Gomes. Departamento de Bioquímica. Laboratório de Interação de Tripanosomatídeos e Vetores. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Farmanguinhos. Departamento de Química de Produtos Naturais. Laboratório de Proteases e Inibidores de Proteases de Origem Natural. Rio de Janeiro, RJ, Brasil.
Abstract: It has been reported that serine peptidase activities of Trypanosoma cruzi play crucial roles in parasite dissemination and host cell invasion and therefore their inhibition could affect the progress of Chagas disease. The present study investigates the interference of the Stichodactyla helianthus Kunitz-type serine protease inhibitor (ShPI-I), a 55-amino acid peptide, in T. cruzi serine peptidase activities, parasite viability, and parasite morphology. The effect of this peptide was also studied in Leishmania amazonensis promastigotes and it was proved to be a powerful inhibitor of serine proteases activities and the parasite viability. The ultrastructural alterations caused by ShPI-I included vesiculation of the flagellar pocket membrane and the appearance of a cytoplasmic vesicle that resembles an autophagic vacuole. ShPI-I, which showed itself to be an important T. cruzi serine peptidase inhibitor, reduced the parasite viability, in a dose and time dependent manner. The maximum effect of peptide on T. cruzi viability was observed when ShPI-I at 1×10(-5)M was incubated for 24 and 48h which killed completely both metacyclic trypomastigote and epimastigote forms. At 1×10(-6)M ShPI-I, in the same periods of time, reduced parasite viability about 91-95% respectively. Ultrastructural analysis demonstrated the formation of concentric membranar structures especially in the cytosol, involving organelles and small vesicles. Profiles of endoplasmic reticulum were also detected, surrounding cytosolic vesicles that resembled autophagic vacuoles. These results suggest that serine peptidases are important in T. cruzi physiology since the inhibition of their activity killed parasites in vitro as well as inducing important morphological alterations. Protease inhibitors thus appear to have a potential role as anti-trypanosomatidal agents.
Keywords: Trypanosoma cruzi
ShPI-I
Peptidase inhibition
Cell viability
Electron microscopy
Chagas Disease
keywords: Trypanosoma cruzi
Doença de Chagas
Viabilidade celular
Microscopia eletrônica
inibidor da peptidase
Issue Date: 2013
Publisher: Elsevier
Citation: NOGUEIRA, Natália Pereira de Almeida; et al. Effects of a marine serine protease inhibitor on viability and morphology of Trypanosoma cruzi, the agent of Chagas disease. Acta Tropica, v.128, n.1, p.27-35, Oct. 2013.
DOI: 10.1016/j.actatropica.2013.05.013
ISSN: 0001-706X
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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