Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/31687
Title: Treatment of Trypanosoma cruzi with 2-bromopalmitate alters morphology, endocytosis, differentiation and infectivity
Authors: Batista, Cassiano Martin
Kessler, Rafael Luis
Eger, Iriane
Soares, Maurilio José
Affilliation: Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Celular. Curitiba, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Genômica Funcional. Curitiba, PR, Brasil. / Instituto de Biologia Molecular do Paraná. Laboratório de Biotecnologia Celular de Mamíferos. Curitiba, PR, Brasil.
Universidade Estadual de Ponta Grossa. Departamento de Biologia Geral. Ponta Grossa, PR, Brasil.
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Biologia Celular. Curitiba, PR, Brasil.
Abstract: The palmitate analogue 2-bromopalmitate (2-BP) is a non-selective membrane tethered cysteine alkylator of many membrane-associated enzymes that in the last years emerged as a general inhibitor of protein S-palmitoylation. Palmitoylation is a post-translational protein modification that adds palmitic acid to a cysteine residue through a thioester linkage, promoting membrane localization, protein stability, regulation of enzymatic activity, and the epigenetic regulation of gene expression. Little is known on such important process in the pathogenic protozoan Trypanosoma cruzi, the etiological agent of Chagas disease. The effect of 2-BP was analyzed on different developmental forms of Trypanosoma cruzi. The IC50/48 h value for culture epimastigotes was estimated as 130 μM. The IC50/24 h value for metacyclic trypomastigotes was 216 nM, while for intracellular amastigotes it was 242 μM and for cell derived trypomasigotes was 262 μM (IC50/24 h). Our data showed that 2-BP altered T. cruzi: 1) morphology, as assessed by bright field, scanning and transmission electron microscopy; 2) mitochondrial membrane potential, as shown by flow cytometry after incubation with rhodamine-123; 3) endocytosis, as seen after incubation with transferrin or albumin and analysis by flow cytometry/fluorescence microscopy; 4) in vitro metacyclogenesis; and 5) infectivity, as shown by host cell infection assays. On the other hand, lipid stress by incubation with palmitate did not alter epimastigote growth, metacyclic trypomastigotes viability or trypomastigote infectivity. Our results indicate that 2-BP inhibits key cellular processes of T. cruzi that may be regulated by palmitoylation of vital proteins and suggest a metacyclic trypomastigote unique target dependency during the parasite development.
Keywords: Cell Differentiation
Endocytosis
Lipoylation
2-Bromopalmitate
Chagas Disease
Keywords in spanish: Diferenciación Celular
Endocitosis
Lipoilación
keywords: Trypanosoma cruzi
DeCS: Diferenciação Celular
Endocitose
Lipoilação
Doença de Chagas
Issue Date: 2018
Publisher: BMC
Citation: BATISTA, Cassiano Martin et al. Treatment of Trypanosoma cruzi with 2-bromopalmitate alters morphology, endocytosis, differentiation and infectivity. BMC Cell Biology, v. 19, n. 19, p. 1-16, 2018.
DOI: 10.1186/s12860-018-0170-3
ISSN: 1471-2121
Copyright: open access
Appears in Collections:PR - ICC - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
s12860-018.pdf4.06 MBAdobe PDFView/Open



FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.