Author | Fonseca, Maisa Santos da | |
Author | Comini, Marcelo A. | |
Author | Resende, Bethânia Vaz de | |
Author | Santi, Ana Maria Murta | |
Author | Zoboli, Antônio P. | |
Author | Moreira, Douglas de Souza | |
Author | Murta, Silvane Maria Fonseca | |
Access date | 2018-06-07T16:54:11Z | |
Available date | 2018-06-07T16:54:11Z | |
Document date | 2017 | |
Citation | FONSECA, Maisa Santos da et al. Ornithine decarboxylase or gamma-glutamylcysteine synthetase overexpression protects Leishmania (Vianna) guyanensis against antimony. Experimental Parasitology, v. 175, p. 36-43, 2017. | pt_BR |
ISSN | 0014-4894 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/26776 | |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | restricted access | pt_BR |
Subject in Portuguese | Leishmania guyanensis | pt_BR |
Subject in Portuguese | Ornithine decarboxylase | pt_BR |
Title | Ornithine decarboxylase or gamma-glutamylcysteine synthetase overexpression protects Leishmania (Vianna) guyanensis against antimony | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.exppara.2017.02.001 | |
Abstract | Trypanosomatids present a unique mechanism for detoxification of peroxides that is dependent on trypanothione (bisglutathionylspermidine). Ornithine decarboxylase (ODC) and γ-glutamylcysteine synthetase (GSH1) produce molecules that are direct precursors of trypanothione. In this study, Leishmania guyanensis odc and gsh1 overexpressor cell lines were generated to investigate the contribution of these genes to the trivalent antimony (SbIII)-resistance phenotype. The ODC- or GSH1-overexpressors parasites presented an increase of two and four-fold in SbIII-resistance index, respectively, when compared with the wild-type line. Pharmacological inhibition of ODC and GSH1 with the specific inhibitors α-difluoromethylornithine (DFMO) and buthionine sulfoximine (BSO), respectively, increased the antileishmanial effect of SbIII in all cell lines. However, the ODC- and GSH1-overexpressor were still more resistant to SbIII than the parental cell line. Together, our data shows that modulation of ODC and GSH1 levels and activity is sufficient to affect L. guyanensis susceptibility to SbIII, and confirms a role of these genes in the SbIII-resistance phenotype. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Institut Pasteur de Montevideo. Laboratorio de Biología Redox de Tripanosomátidos. Montevideo, Uruguay. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto René Rachou. Laboratório de Parasitologia Celular e Molecular. Belo Horizonte, MG, Brasil. | pt_BR |
Subject | Leishmania guyanensis | pt_BR |
Subject | Ornithine decarboxylase | pt_BR |
Subject | Gamma-glutamylcysteine synthetase | pt_BR |
Subject | Antimony-resistance | pt_BR |
Subject | Trypanothione | pt_BR |
Embargo date | 2026-01-01 | |