Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/30842
Title: Naphthoimidazoles promote different death phenotypes in Trypanosoma cruzi
Authors: Menna-Barreto, Rubem F.. S
Corrêa, J.R.
Cascabulho, C. M.
Fernandes, M. C.
Pinto, A. V.
Soares, M. J.
Castro, Solange L. de
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Estrutural. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.
Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Núcleo de Pesquisas em Produtos Naturais. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Celular. Rio de Janeiro, RJ. Brasil.
Abstract: In a screening of 65 derivatives of natural quinones using bloodstream trypomastigotes of Trypanosoma cruzi, the 3 naphthoimidazoles derived from beta-lapachone - N1, N2 and N3--were selected as the most active. Investigation of their mode of action led to the characterization of mitochondrion, reservosomes and DNA as their main targets, and stimulated further studies on death pathways. Ultrastructural analysis revealed both autophagic (autophagosomes) and apoptotic-like (membrane blebbing) phenotypes. Flow cytometry analysis showed, in N2-treated trypomastigotes, a small increase of phosphatidylserine exposure, and a large increase in the percentage of necrosis, caused by N1 or N2. These death phenotypes were not detected in treated epimastigotes. The strong increase in labelling of monodansyl cadaverine, the inhibition of the death process by wortmannin or 3-methyladenine, the overexpression of ATG genes in treated epimastigotes, together with ultrastructural evidence point to autophagy as the predominant phenotype induced by the naphthoimidazoles. However, there are other pathways occurring concomitantly with variable intensities, justifying the need to detail the molecular features involved.
Keywords: Trypanosoma cruzi
naphthoimidazoles
death pathways
autophagy
keywords: Trypanosoma cruzi
Autofagia
naftoimidazoles
caminhos da morte
Issue Date: 2009
Publisher: Cambridge University Press
Citation: MENNA-BARRETO, R. F. S. et al. Naphthoimidazoles promote different death phenotypes in Trypanosoma cruzi. Parasitology, v.136, p.499-510, 2009.
DOI: 10.1017/S0031182009005745
ISSN: 0031-1820
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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