Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone

Autores
Garavaglia, Patricia A; Rubio, María Fernanda; Laverrière, Marc; Tasso, Laura Mónica; Fichera, Laura E.; Cannata, Joaquín J B; García, Gabriela Andrea
Año de publicación
2018
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Fil: Garavaglia, Patricia A ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Rubio, María Fernanda. Laboratorio de Biología Molecular y Apoptosis,Instituto de Investigaciones Médicas Alfredo Lanari (IDIM-CONICET),Universidad de Buenos Aires,Ciudad de Buenos Aires (1427); Argentina.
Fil: Laverrière, Marc. Instituto de Investigaciones Biotecnológicas (IIB-INTECH),Universidad Nacional de General San Martín-CONICET,San Martín (1650),Prov. Buenos Aires; Argentina.
Fil: Tasso, Laura Mónica. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Fichera, Laura E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Cannata, Joaquín J B. Instituto de Investigaciones Biotecnológicas (IIB-INTECH),Universidad Nacional de General San Martín-CONICET,San Martín (1650),Prov. Buenos Aires; Argentina.
Fil: García, Gabriela Andrea. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Several ortho-naphthoquinones (o-NQs) have trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Previously, we demonstrated that the aldo-keto reductase from this parasite (TcAKR) reduces o-NQs, such as β-lapachone (β-Lap) and 9,10-phenanthrenequinone (9,10-PQ), with concomitant reactive oxygen species (ROS) production. Recent characterization of TcAKR activity and expression in two T. cruzi strains, CL Brener and Nicaragua, showed that TcAKR expression is 2.2-fold higher in CL Brener than in Nicaragua. Here, we studied the trypanocidal effect and induction of several death phenotypes by β-Lap and 9,10-PQ in epimastigotes of these two strains. The CL Brener strain was more resistant to both o-NQs than Nicaragua, indicating that greater TcAKR activity is unlikely to be a major influence on o-NQ toxicity. Evaluation of changes in ROS production, mitochondrial membrane potential, phosphatidylserine exposure and monodansylcadaverine labelling evidenced that β-Lap and 9,10-PQ induce different death phenotypes depending on the combination of drug and T. cruzi strain analysed. To study whether TcAKR participates in o-NQ activation in intact parasites, β-Lap and 9,10-PQ trypanocidal effect was next evaluated in TcAKR-overexpressing parasites. Only β-Lap was more effective and induced greater ROS production in TcAKR-overexpressing epimastigotes than in controls, suggesting that TcAKR may participate in β-Lap activation.
Fuente
Parasitology 2018; 145(9):1251-1259.
Materia
Muerte celular regulada
Enfermedad de Chagas
Quimioterapia
Nivel de accesibilidad
acceso abierto
Condiciones de uso
none
Repositorio
Sistema de Gestión del Conocimiento ANLIS MALBRÁN
Institución
Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
OAI Identificador
oai:sgc.anlis.gob.ar:123456789/1416

id SGCANLIS_9b5bae6019e75966433431d794de9f15
oai_identifier_str oai:sgc.anlis.gob.ar:123456789/1416
network_acronym_str SGCANLIS
repository_id_str a
network_name_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
spelling Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachoneGaravaglia, Patricia ARubio, María FernandaLaverrière, MarcTasso, Laura MónicaFichera, Laura E.Cannata, Joaquín J BGarcía, Gabriela AndreaMuerte celular reguladaEnfermedad de ChagasQuimioterapiaFil: Garavaglia, Patricia A ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Rubio, María Fernanda. Laboratorio de Biología Molecular y Apoptosis,Instituto de Investigaciones Médicas Alfredo Lanari (IDIM-CONICET),Universidad de Buenos Aires,Ciudad de Buenos Aires (1427); Argentina.Fil: Laverrière, Marc. Instituto de Investigaciones Biotecnológicas (IIB-INTECH),Universidad Nacional de General San Martín-CONICET,San Martín (1650),Prov. Buenos Aires; Argentina.Fil: Tasso, Laura Mónica. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Fichera, Laura E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Cannata, Joaquín J B. Instituto de Investigaciones Biotecnológicas (IIB-INTECH),Universidad Nacional de General San Martín-CONICET,San Martín (1650),Prov. Buenos Aires; Argentina.Fil: García, Gabriela Andrea. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Several ortho-naphthoquinones (o-NQs) have trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Previously, we demonstrated that the aldo-keto reductase from this parasite (TcAKR) reduces o-NQs, such as β-lapachone (β-Lap) and 9,10-phenanthrenequinone (9,10-PQ), with concomitant reactive oxygen species (ROS) production. Recent characterization of TcAKR activity and expression in two T. cruzi strains, CL Brener and Nicaragua, showed that TcAKR expression is 2.2-fold higher in CL Brener than in Nicaragua. Here, we studied the trypanocidal effect and induction of several death phenotypes by β-Lap and 9,10-PQ in epimastigotes of these two strains. The CL Brener strain was more resistant to both o-NQs than Nicaragua, indicating that greater TcAKR activity is unlikely to be a major influence on o-NQ toxicity. Evaluation of changes in ROS production, mitochondrial membrane potential, phosphatidylserine exposure and monodansylcadaverine labelling evidenced that β-Lap and 9,10-PQ induce different death phenotypes depending on the combination of drug and T. cruzi strain analysed. To study whether TcAKR participates in o-NQ activation in intact parasites, β-Lap and 9,10-PQ trypanocidal effect was next evaluated in TcAKR-overexpressing parasites. Only β-Lap was more effective and induced greater ROS production in TcAKR-overexpressing epimastigotes than in controls, suggesting that TcAKR may participate in β-Lap activation.Cambridge University Press2018info:ar-repo/semantics/articuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdf1469-8161http://sgc.anlis.gob.ar/handle/123456789/141610.1017/S0031182018000045Parasitology 2018; 145(9):1251-1259.reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁNinstname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"instacron:ANLISParasitologynoneinfo:eu-repo/semantics/openAccesseng2025-09-04T11:16:50Zoai:sgc.anlis.gob.ar:123456789/1416Institucionalhttp://sgc.anlis.gob.ar/Organismo científico-tecnológicoNo correspondehttp://sgc.anlis.gob.ar/oai/biblioteca@anlis.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:a2025-09-04 11:16:50.82Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"false
dc.title.none.fl_str_mv Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone
title Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone
spellingShingle Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone
Garavaglia, Patricia A
Muerte celular regulada
Enfermedad de Chagas
Quimioterapia
title_short Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone
title_full Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone
title_fullStr Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone
title_full_unstemmed Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone
title_sort Trypanosoma cruzi: death phenotypes induced by ortho-naphthoquinone substrates of the aldo-keto reductase (TcAKR). Role of this enzyme in the mechanism of action of β-lapachone
dc.creator.none.fl_str_mv Garavaglia, Patricia A
Rubio, María Fernanda
Laverrière, Marc
Tasso, Laura Mónica
Fichera, Laura E.
Cannata, Joaquín J B
García, Gabriela Andrea
author Garavaglia, Patricia A
author_facet Garavaglia, Patricia A
Rubio, María Fernanda
Laverrière, Marc
Tasso, Laura Mónica
Fichera, Laura E.
Cannata, Joaquín J B
García, Gabriela Andrea
author_role author
author2 Rubio, María Fernanda
Laverrière, Marc
Tasso, Laura Mónica
Fichera, Laura E.
Cannata, Joaquín J B
García, Gabriela Andrea
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Muerte celular regulada
Enfermedad de Chagas
Quimioterapia
topic Muerte celular regulada
Enfermedad de Chagas
Quimioterapia
dc.description.none.fl_txt_mv Fil: Garavaglia, Patricia A ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Rubio, María Fernanda. Laboratorio de Biología Molecular y Apoptosis,Instituto de Investigaciones Médicas Alfredo Lanari (IDIM-CONICET),Universidad de Buenos Aires,Ciudad de Buenos Aires (1427); Argentina.
Fil: Laverrière, Marc. Instituto de Investigaciones Biotecnológicas (IIB-INTECH),Universidad Nacional de General San Martín-CONICET,San Martín (1650),Prov. Buenos Aires; Argentina.
Fil: Tasso, Laura Mónica. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Fichera, Laura E. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Fil: Cannata, Joaquín J B. Instituto de Investigaciones Biotecnológicas (IIB-INTECH),Universidad Nacional de General San Martín-CONICET,San Martín (1650),Prov. Buenos Aires; Argentina.
Fil: García, Gabriela Andrea. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
Several ortho-naphthoquinones (o-NQs) have trypanocidal activity against Trypanosoma cruzi, the aetiological agent of Chagas disease. Previously, we demonstrated that the aldo-keto reductase from this parasite (TcAKR) reduces o-NQs, such as β-lapachone (β-Lap) and 9,10-phenanthrenequinone (9,10-PQ), with concomitant reactive oxygen species (ROS) production. Recent characterization of TcAKR activity and expression in two T. cruzi strains, CL Brener and Nicaragua, showed that TcAKR expression is 2.2-fold higher in CL Brener than in Nicaragua. Here, we studied the trypanocidal effect and induction of several death phenotypes by β-Lap and 9,10-PQ in epimastigotes of these two strains. The CL Brener strain was more resistant to both o-NQs than Nicaragua, indicating that greater TcAKR activity is unlikely to be a major influence on o-NQ toxicity. Evaluation of changes in ROS production, mitochondrial membrane potential, phosphatidylserine exposure and monodansylcadaverine labelling evidenced that β-Lap and 9,10-PQ induce different death phenotypes depending on the combination of drug and T. cruzi strain analysed. To study whether TcAKR participates in o-NQ activation in intact parasites, β-Lap and 9,10-PQ trypanocidal effect was next evaluated in TcAKR-overexpressing parasites. Only β-Lap was more effective and induced greater ROS production in TcAKR-overexpressing epimastigotes than in controls, suggesting that TcAKR may participate in β-Lap activation.
description Fil: Garavaglia, Patricia A ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
publishDate 2018
dc.date.none.fl_str_mv 2018
dc.type.none.fl_str_mv info:ar-repo/semantics/articulo
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv 1469-8161
http://sgc.anlis.gob.ar/handle/123456789/1416
10.1017/S0031182018000045
identifier_str_mv 1469-8161
10.1017/S0031182018000045
url http://sgc.anlis.gob.ar/handle/123456789/1416
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Parasitology
dc.rights.none.fl_str_mv none
info:eu-repo/semantics/openAccess
rights_invalid_str_mv none
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Cambridge University Press
publisher.none.fl_str_mv Cambridge University Press
dc.source.none.fl_str_mv Parasitology 2018; 145(9):1251-1259.
reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁN
instname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron:ANLIS
reponame_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
collection Sistema de Gestión del Conocimiento ANLIS MALBRÁN
instname_str Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron_str ANLIS
institution ANLIS
repository.name.fl_str_mv Sistema de Gestión del Conocimiento ANLIS MALBRÁN - Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
repository.mail.fl_str_mv biblioteca@anlis.gov.ar
_version_ 1842344421141512192
score 12.623145