Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism

Fil: Garavaglia, Patricia Andrea. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.

Bibliographic Details
Authors: Garavaglia, Patricia A, Laverrière, Marc, Cannata, Joaquín J B, García, Gabriela Andrea
Format: article
Status:Published version
Publication Date:2016
Country:Argentina
Institution:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
Repository:Sistema de Gestión del Conocimiento ANLIS MALBRÁN
Language:English
OAI Identifier:oai:sgc.anlis.gob.ar:123456789/1431
Online Access:http://sgc.anlis.gob.ar/handle/123456789/1431
Access Level:Open access
Keyword:Trypanosoma cruzi
Enfermedad de Chagas
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spelling Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole MetabolismGaravaglia, Patricia ALaverrière, MarcCannata, Joaquín J BGarcía, Gabriela AndreaTrypanosoma cruziEnfermedad de ChagasFil: Garavaglia, Patricia Andrea. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Fil: Cannata, Joaquín J B. Instituto de Investigaciones Biotecnológicas, Universidad Nacional de General San Martín-CONICET; Argentina.Fil: Laverriere, Marc. Instituto de Investigaciones Biotecnológicas, Universidad Nacional de General San Martín-CONICET; Argentina.Fil: Garcia, Gabriela Andrea. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.Benznidazole (Bz), the drug used for treatment of Chagas' disease (caused by the protozoan Trypanosoma cruzi), is activated by a parasitic NADH-dependent type I nitroreductase (NTR I). However, several studies have shown that other enzymes are involved. The aim of this study was to evaluate whether the aldo-keto reductase from T. cruzi (TcAKR), a NADPH-dependent oxido-reductase previously described by our group, uses Bz as the substrate. We demonstrated that both recombinant and native TcAKR enzymes reduce Bz by using NADPH, but not NADH, as a cofactor. TcAKR-overexpressing epimastigotes showed higher NADPH-dependent Bz reductase activity and a 50% inhibitory concentration (IC50) value for Bz 1.8-fold higher than that of the controls, suggesting that TcAKR is involved in Bz detoxification instead of activation. To understand the role of TcAKR in Bz metabolism, we studied TcAKR expression and NADPH/NADH-dependent Bz reductase activities in two T. cruzi strains with differential susceptibility to Bz: CL Brener and Nicaragua. Taking into account the results obtained with TcAKR-overexpressing epimastigotes, we expected the more resistant strain, Nicaragua, to have higher TcAKR levels than CL Brener. However, the results were the opposite. CL Brener showed 2-fold higher TcAKR expression and 5.7-fold higher NADPH-Bz reduction than the Nicaragua strain. In addition, NADH-dependent Bz reductase activity, characteristic of NTR I, was also higher in CL Brener than in Nicaragua. We conclude that although TcAKR uses Bz as the substrate, TcAKR activity is not a determinant of Bz resistance in wild-type strains and may be overcome by other enzymes involved in Bz activation, such as NADPH- and NADH-dependent reductases.2016-04-22info:ar-repo/semantics/articuloinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdf0066-4804http://sgc.anlis.gob.ar/handle/123456789/143110.1128/AAC.02185-152016; 60(5):2664-2670reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁNinstname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"instacron:ANLISAntimicrobial agents and chemotherapyenginfo:eu-repo/semantics/openAccess2024-05-10T11:51:57Zoai:sgc.anlis.gob.ar:123456789/1431Institucionalhttp://sgc.anlis.gob.ar/Organismo científico-tecnológicoNo correspondehttp://sgc.anlis.gob.ar/oai/biblioteca@anlis.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:a2024-05-10 11:51:57.773Sistema 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 Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism
title Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism
spellingShingle Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism
Garavaglia, Patricia A
Trypanosoma cruzi
Enfermedad de Chagas
title_short Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism
title_full Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism
title_fullStr Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism
title_full_unstemmed Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism
title_sort Putative Role of the Aldo-Keto Reductase from Trypanosoma cruzi in Benznidazole Metabolism
dc.creator.none.fl_str_mv Garavaglia, Patricia A
Laverrière, Marc
Cannata, Joaquín J B
García, Gabriela Andrea
author Garavaglia, Patricia A
author_facet Garavaglia, Patricia A
Laverrière, Marc
Cannata, Joaquín J B
García, Gabriela Andrea
author_role author
author2 Laverrière, Marc
Cannata, Joaquín J B
García, Gabriela Andrea
author2_role author
author
author
dc.subject.none.fl_str_mv Trypanosoma cruzi
Enfermedad de Chagas
topic Trypanosoma cruzi
Enfermedad de Chagas
description Fil: Garavaglia, Patricia Andrea. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Parasitología; Argentina.
publishDate 2016
dc.date.none.fl_str_mv 2016-04-22
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 0066-4804
http://sgc.anlis.gob.ar/handle/123456789/1431
10.1128/AAC.02185-15
identifier_str_mv 0066-4804
10.1128/AAC.02185-15
url http://sgc.anlis.gob.ar/handle/123456789/1431
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Antimicrobial agents and chemotherapy
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv 2016; 60(5):2664-2670
reponame:Sistema de Gestión del Conocimiento ANLIS MALBRÁN
instname:Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron:ANLIS
instname_str Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"
instacron_str ANLIS
institution ANLIS
reponame_str Sistema de Gestión del Conocimiento ANLIS MALBRÁN
collection Sistema de Gestión del Conocimiento ANLIS MALBRÁN
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
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