Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole

Autores
Rêgo, Juciane Vaz; Duarte, Ana Paula; Liarte, Daniel Barbosa; de Carvalho Sousa, Francirlene; Barreto, Humberto Medeiros; Bua, Jacqueline Elena; Romanha, Alvaro José; Rádis Baptista, Gandhi; Murta, Silvane Maria Fonseca
Año de publicación
2015
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Cyclophilin (TcCyP19), a peptidyl-prolyl cis/trans isomerase, is a key molecule with diverse biological functions that include roles in molecular chaperoning, stress response, immune modulation, and signal transduction. In this respect, TcCyP19 could serve as a potential drug target in diseasecausing parasites. Previous studies employing proteomics techniques have shown that the TcCyP19 isoform was more abundant in a benznidazole (BZ)-resistant Trypanosoma cruzi population than in its susceptible counterpart. In this study, TcCyP19 has been characterized in BZ-susceptible and BZresistant T. cruzi populations. Phylogenetic analysis revealed a clear dichotomy between Cyphophilin A (CyPA) sequences from trypanosomatids and mammals. Sequencing analysis revealed that the amino acid sequences of TcCyP19 were identical among the T. cruzi samples analyzed. Southern blot analysis showed that TcCyP19 is a single-copy gene, located in chromosomal bands varying in size from 0.68 to 2.2 Mb, depending on the strain of T. cruzi. Northern blot and qPCR indicated that the levels of TcCyP19 mRNA were two-fold higher in drug-resistant T. cruzi populations than in their drugsusceptible counterparts. Similarly, as determined by two-dimensional gel electrophoresis immunoblot, the expression of TcCyP19 protein was increased to the same degree in BZ-resistant T. cruzi populations. No differences in TcCyP19 mRNA and protein expression levels were observed between the susceptible and the naturally resistant T. cruzi strains analyzed. Taken together, these data indicate that cyclophilin TcCyP19 expression is up-regulated at both transcriptional and translational levels in T. cruzi populations that were in vitro-induced and in vivo-selected for resistance to BZ.
Fil: Rêgo, Juciane Vaz. Universidade Federal Do Piaui.; Brasil
Fil: Duarte, Ana Paula. Fundación Oswaldo Cruz; Brasil
Fil: Liarte, Daniel Barbosa. Universidade Federal Do Piaui.; Brasil
Fil: de Carvalho Sousa, Francirlene. Universidade Federal Do Piaui.; Brasil
Fil: Barreto, Humberto Medeiros. Universidade Federal Do Piaui.; Brasil
Fil: Bua, Jacqueline Elena. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Romanha, Alvaro José. Fundación Oswaldo Cruz; Brasil
Fil: Rádis Baptista, Gandhi. Universidade Federal Do Piaui.; Brasil
Fil: Murta, Silvane Maria Fonseca. Universidade Federal Do Piaui.; Brasil
Materia
Trypanosoma cruzi
Ciclofilinas
resistencia benznidazol
sobreexpresion de TcCyP19
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/107611

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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazoleRêgo, Juciane VazDuarte, Ana PaulaLiarte, Daniel Barbosade Carvalho Sousa, FrancirleneBarreto, Humberto MedeirosBua, Jacqueline ElenaRomanha, Alvaro JoséRádis Baptista, GandhiMurta, Silvane Maria FonsecaTrypanosoma cruziCiclofilinasresistencia benznidazolsobreexpresion de TcCyP19https://purl.org/becyt/ford/3.4https://purl.org/becyt/ford/3Cyclophilin (TcCyP19), a peptidyl-prolyl cis/trans isomerase, is a key molecule with diverse biological functions that include roles in molecular chaperoning, stress response, immune modulation, and signal transduction. In this respect, TcCyP19 could serve as a potential drug target in diseasecausing parasites. Previous studies employing proteomics techniques have shown that the TcCyP19 isoform was more abundant in a benznidazole (BZ)-resistant Trypanosoma cruzi population than in its susceptible counterpart. In this study, TcCyP19 has been characterized in BZ-susceptible and BZresistant T. cruzi populations. Phylogenetic analysis revealed a clear dichotomy between Cyphophilin A (CyPA) sequences from trypanosomatids and mammals. Sequencing analysis revealed that the amino acid sequences of TcCyP19 were identical among the T. cruzi samples analyzed. Southern blot analysis showed that TcCyP19 is a single-copy gene, located in chromosomal bands varying in size from 0.68 to 2.2 Mb, depending on the strain of T. cruzi. Northern blot and qPCR indicated that the levels of TcCyP19 mRNA were two-fold higher in drug-resistant T. cruzi populations than in their drugsusceptible counterparts. Similarly, as determined by two-dimensional gel electrophoresis immunoblot, the expression of TcCyP19 protein was increased to the same degree in BZ-resistant T. cruzi populations. No differences in TcCyP19 mRNA and protein expression levels were observed between the susceptible and the naturally resistant T. cruzi strains analyzed. Taken together, these data indicate that cyclophilin TcCyP19 expression is up-regulated at both transcriptional and translational levels in T. cruzi populations that were in vitro-induced and in vivo-selected for resistance to BZ.Fil: Rêgo, Juciane Vaz. Universidade Federal Do Piaui.; BrasilFil: Duarte, Ana Paula. Fundación Oswaldo Cruz; BrasilFil: Liarte, Daniel Barbosa. Universidade Federal Do Piaui.; BrasilFil: de Carvalho Sousa, Francirlene. Universidade Federal Do Piaui.; BrasilFil: Barreto, Humberto Medeiros. Universidade Federal Do Piaui.; BrasilFil: Bua, Jacqueline Elena. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Romanha, Alvaro José. Fundación Oswaldo Cruz; BrasilFil: Rádis Baptista, Gandhi. Universidade Federal Do Piaui.; BrasilFil: Murta, Silvane Maria Fonseca. Universidade Federal Do Piaui.; BrasilAcademic Press Inc Elsevier Science2015-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/107611Rêgo, Juciane Vaz; Duarte, Ana Paula; Liarte, Daniel Barbosa; de Carvalho Sousa, Francirlene; Barreto, Humberto Medeiros; et al.; Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole; Academic Press Inc Elsevier Science; Experimental Parasitology; 148; 1-2015; 73-800014-4894CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/www.sciencedirect.com/science/article/abs/pii/S0014489414002689info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2014.11.007info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:58:48Zoai:ri.conicet.gov.ar:11336/107611instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:58:49.005CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole
title Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole
spellingShingle Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole
Rêgo, Juciane Vaz
Trypanosoma cruzi
Ciclofilinas
resistencia benznidazol
sobreexpresion de TcCyP19
title_short Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole
title_full Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole
title_fullStr Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole
title_full_unstemmed Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole
title_sort Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole
dc.creator.none.fl_str_mv Rêgo, Juciane Vaz
Duarte, Ana Paula
Liarte, Daniel Barbosa
de Carvalho Sousa, Francirlene
Barreto, Humberto Medeiros
Bua, Jacqueline Elena
Romanha, Alvaro José
Rádis Baptista, Gandhi
Murta, Silvane Maria Fonseca
author Rêgo, Juciane Vaz
author_facet Rêgo, Juciane Vaz
Duarte, Ana Paula
Liarte, Daniel Barbosa
de Carvalho Sousa, Francirlene
Barreto, Humberto Medeiros
Bua, Jacqueline Elena
Romanha, Alvaro José
Rádis Baptista, Gandhi
Murta, Silvane Maria Fonseca
author_role author
author2 Duarte, Ana Paula
Liarte, Daniel Barbosa
de Carvalho Sousa, Francirlene
Barreto, Humberto Medeiros
Bua, Jacqueline Elena
Romanha, Alvaro José
Rádis Baptista, Gandhi
Murta, Silvane Maria Fonseca
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Trypanosoma cruzi
Ciclofilinas
resistencia benznidazol
sobreexpresion de TcCyP19
topic Trypanosoma cruzi
Ciclofilinas
resistencia benznidazol
sobreexpresion de TcCyP19
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.4
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Cyclophilin (TcCyP19), a peptidyl-prolyl cis/trans isomerase, is a key molecule with diverse biological functions that include roles in molecular chaperoning, stress response, immune modulation, and signal transduction. In this respect, TcCyP19 could serve as a potential drug target in diseasecausing parasites. Previous studies employing proteomics techniques have shown that the TcCyP19 isoform was more abundant in a benznidazole (BZ)-resistant Trypanosoma cruzi population than in its susceptible counterpart. In this study, TcCyP19 has been characterized in BZ-susceptible and BZresistant T. cruzi populations. Phylogenetic analysis revealed a clear dichotomy between Cyphophilin A (CyPA) sequences from trypanosomatids and mammals. Sequencing analysis revealed that the amino acid sequences of TcCyP19 were identical among the T. cruzi samples analyzed. Southern blot analysis showed that TcCyP19 is a single-copy gene, located in chromosomal bands varying in size from 0.68 to 2.2 Mb, depending on the strain of T. cruzi. Northern blot and qPCR indicated that the levels of TcCyP19 mRNA were two-fold higher in drug-resistant T. cruzi populations than in their drugsusceptible counterparts. Similarly, as determined by two-dimensional gel electrophoresis immunoblot, the expression of TcCyP19 protein was increased to the same degree in BZ-resistant T. cruzi populations. No differences in TcCyP19 mRNA and protein expression levels were observed between the susceptible and the naturally resistant T. cruzi strains analyzed. Taken together, these data indicate that cyclophilin TcCyP19 expression is up-regulated at both transcriptional and translational levels in T. cruzi populations that were in vitro-induced and in vivo-selected for resistance to BZ.
Fil: Rêgo, Juciane Vaz. Universidade Federal Do Piaui.; Brasil
Fil: Duarte, Ana Paula. Fundación Oswaldo Cruz; Brasil
Fil: Liarte, Daniel Barbosa. Universidade Federal Do Piaui.; Brasil
Fil: de Carvalho Sousa, Francirlene. Universidade Federal Do Piaui.; Brasil
Fil: Barreto, Humberto Medeiros. Universidade Federal Do Piaui.; Brasil
Fil: Bua, Jacqueline Elena. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud “Dr. C. G. Malbrán”. Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben”; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Romanha, Alvaro José. Fundación Oswaldo Cruz; Brasil
Fil: Rádis Baptista, Gandhi. Universidade Federal Do Piaui.; Brasil
Fil: Murta, Silvane Maria Fonseca. Universidade Federal Do Piaui.; Brasil
description Cyclophilin (TcCyP19), a peptidyl-prolyl cis/trans isomerase, is a key molecule with diverse biological functions that include roles in molecular chaperoning, stress response, immune modulation, and signal transduction. In this respect, TcCyP19 could serve as a potential drug target in diseasecausing parasites. Previous studies employing proteomics techniques have shown that the TcCyP19 isoform was more abundant in a benznidazole (BZ)-resistant Trypanosoma cruzi population than in its susceptible counterpart. In this study, TcCyP19 has been characterized in BZ-susceptible and BZresistant T. cruzi populations. Phylogenetic analysis revealed a clear dichotomy between Cyphophilin A (CyPA) sequences from trypanosomatids and mammals. Sequencing analysis revealed that the amino acid sequences of TcCyP19 were identical among the T. cruzi samples analyzed. Southern blot analysis showed that TcCyP19 is a single-copy gene, located in chromosomal bands varying in size from 0.68 to 2.2 Mb, depending on the strain of T. cruzi. Northern blot and qPCR indicated that the levels of TcCyP19 mRNA were two-fold higher in drug-resistant T. cruzi populations than in their drugsusceptible counterparts. Similarly, as determined by two-dimensional gel electrophoresis immunoblot, the expression of TcCyP19 protein was increased to the same degree in BZ-resistant T. cruzi populations. No differences in TcCyP19 mRNA and protein expression levels were observed between the susceptible and the naturally resistant T. cruzi strains analyzed. Taken together, these data indicate that cyclophilin TcCyP19 expression is up-regulated at both transcriptional and translational levels in T. cruzi populations that were in vitro-induced and in vivo-selected for resistance to BZ.
publishDate 2015
dc.date.none.fl_str_mv 2015-01
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/107611
Rêgo, Juciane Vaz; Duarte, Ana Paula; Liarte, Daniel Barbosa; de Carvalho Sousa, Francirlene; Barreto, Humberto Medeiros; et al.; Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole; Academic Press Inc Elsevier Science; Experimental Parasitology; 148; 1-2015; 73-80
0014-4894
CONICET Digital
CONICET
url http://hdl.handle.net/11336/107611
identifier_str_mv Rêgo, Juciane Vaz; Duarte, Ana Paula; Liarte, Daniel Barbosa; de Carvalho Sousa, Francirlene; Barreto, Humberto Medeiros; et al.; Molecular characterization of Cyclophilin (TcCyP19) in Trypanosoma cruzi populations susceptible and resistant to benznidazole; Academic Press Inc Elsevier Science; Experimental Parasitology; 148; 1-2015; 73-80
0014-4894
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/www.sciencedirect.com/science/article/abs/pii/S0014489414002689
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.exppara.2014.11.007
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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