Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/11529
Title: P-glycoprotein efflux pump plays an important role in Trypanosoma cruzi drug resistance
Authors: Campos, Mônica Caroline Oliveira
Pinto, Denise Barçante Castro
Ribeiro, Grazielle Alves
Pinho, Márcia Moreira Berredo
Gomes, Leonardo Henrique Ferreira
Bellieny, Myrtes Santos da Silva
Goulart, Carla Marins
Echevarria, Aurea
Leon, Leonor Laura
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Boquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Boquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Boquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Microbiologia Celular. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Genômica Funcional e Bioinformática, Rio de Janeiro, RJ, Brasil.
Universidade Federal Rural do Rio de Janeiro, UFRRJ. Departamento de Química. Rio de Janeiro, RJ, Brasil.
Universidade Federal Rural do Rio de Janeiro, UFRRJ. Departamento de Química. Rio de Janeiro, RJ, Brasil
Universidade Federal Rural do Rio de Janeiro, UFRRJ. Departamento de Química. Rio de Janeiro, RJ, Brasil
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Boquímica de Tripanossomatídeos. Rio de Janeiro, RJ, Brasil.
Abstract: Drug resistance in protozoan parasites has been associated with the P-glycoprotein (Pgp), an energydependent efflux pump that transports substances across the membrane. Interestingly, the genes TcPGP1 and TcPGP2 have been described in Trypanosoma cruzi, although the function of these genes has not been fully elucidated. The main goal of this work was to investigate Pgp efflux pump activity and expression in T. cruzi lines submitted to in vitro induced resistance to the compounds 4-N-(2-methoxy styryl)-thiosemicarbazone (2-Meotio) and benznidazole (Bz) and to verify the stability of the resistant phenotypes during the parasite life cycle. We observed that the EC50 values for the treatment of epimastigotes with 2-Meotio or Bz were increased at least 4.7-fold in resistant lines, and this phenotype was maintained in metacyclic trypomastigotes, cell-derived trypomastigotes, and intracellular amastigotes. However, in epimastigotes, 2-Meotio resistance is reversible, but Bz resistance is irreversible. When compared with the parental line, the resistant lines exhibited higher Pgp efflux activity, reversion of the resistant phenotypes in the presence of Pgp inhibitors, cross-resistance with Pgp modulators, higher basal Pgp ATPase activity, and overexpression of the genes TcPGP1 and TcPGP2. In conclusion, the resistance induced in T. cruzi by the compounds 2-Meotio and Bz is maintained during the entire parasite life cycle. Furthermore, our data suggest the participation of the Pgp efflux pump in T. cruzi drug resistance.
Keywords: Trypanosoma cruzi
Drug resistance
P-glycoprotein
DeCS: Trypanosoma cruzi
Resistência a Medicamentos
Glicoproteína P
Issue Date: 2013
Publisher: Springerlink
Citation: CAMPOS, Mònica Caroline Oliveira; et al. P-glycoprotein efflux pump plays an important role in Trypanosoma cruzi drug resistance. Parasitol Res, v.112, n.6, p.2341–2351, 2013.
DOI: 10.1007/s00436-013-3398-z
ISSN: 1432-1955
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

Files in This Item:
File Description SizeFormat 
monica_campos_etal_IOC_2013.pdf441.55 kBAdobe PDF    Request a copy



FacebookTwitterDeliciousLinkedInGoogle BookmarksBibTex Format mendeley Endnote DiggMySpace

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