P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus

Autores
Nicolao, María Celeste; Denegri, Guillermo Maria; Cárcamo, Juan Guillermo; Cumino, Andrea Carina
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
P-glycoprotein (Pgp) is an ATP-dependent transporter involved in the efflux of a wide variety of lipophilic substrates, such as toxins and xenobiotics, out of cells. Pgp expression level is associated with the ineffective therapeutic treatment of cancer cells and microbial pathogens which gives it high clinical importance. Research on these transporters in helminths is limited. This work describes for the first time the Echinococcus granulosus Pgp (Eg-Pgp) expression, in a model cestode parasite and an important human pathogen. Based on calcein efflux assays in the presence of common Pgp modulators, we demonstrated the occurrence of active Eg-Pgp in protoscoleces and metacestodes. Eg-Pgp, which showed a molecular mass of ~130 kDa in western blots, is localized in the suckers and the tegument of control protoscoleces as well as in the subtegument or all parenchymatous cells of protoscoleces treated with Pgp-interfering agents. We also identified five genes encoding Pgp which are constitutively expressed in protoscoleces and metacestodes. We showed that the Eg-pgp1 and Eg-pgp2 transcripts were up-regulated in response to in vitro drug treatment with amiodarone and loperamide, in agreement with the increased polypeptide levels. Finally, in vitro treatment of protoscoleces and metacestodes with trifluoperazine and loperamide was lethal to the parasites. This indicates that both drugs as well as cyclosporine A negatively modulate the E. granulosus Pgp efflux activity, favoring the retention of these drugs in the larval tissue. These events could be associated with the reduction in protoscolex and metacestode viability.
Fil: Nicolao, María Celeste. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Denegri, Guillermo Maria. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cárcamo, Juan Guillermo. Universidad Austral de Chile.; Chile
Fil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina
Materia
Echinococcus Granulosus
Gene Expression
Glycoprotein P
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25778
Acceder
id CONICETDig_4465ecb6d6459f73660db6454b6f9ea6
oai_identifier_str oai:ri.conicet.gov.ar:11336/25778
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosusNicolao, María CelesteDenegri, Guillermo MariaCárcamo, Juan GuillermoCumino, Andrea CarinaEchinococcus GranulosusGene ExpressionGlycoprotein Phttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1P-glycoprotein (Pgp) is an ATP-dependent transporter involved in the efflux of a wide variety of lipophilic substrates, such as toxins and xenobiotics, out of cells. Pgp expression level is associated with the ineffective therapeutic treatment of cancer cells and microbial pathogens which gives it high clinical importance. Research on these transporters in helminths is limited. This work describes for the first time the Echinococcus granulosus Pgp (Eg-Pgp) expression, in a model cestode parasite and an important human pathogen. Based on calcein efflux assays in the presence of common Pgp modulators, we demonstrated the occurrence of active Eg-Pgp in protoscoleces and metacestodes. Eg-Pgp, which showed a molecular mass of ~130 kDa in western blots, is localized in the suckers and the tegument of control protoscoleces as well as in the subtegument or all parenchymatous cells of protoscoleces treated with Pgp-interfering agents. We also identified five genes encoding Pgp which are constitutively expressed in protoscoleces and metacestodes. We showed that the Eg-pgp1 and Eg-pgp2 transcripts were up-regulated in response to in vitro drug treatment with amiodarone and loperamide, in agreement with the increased polypeptide levels. Finally, in vitro treatment of protoscoleces and metacestodes with trifluoperazine and loperamide was lethal to the parasites. This indicates that both drugs as well as cyclosporine A negatively modulate the E. granulosus Pgp efflux activity, favoring the retention of these drugs in the larval tissue. These events could be associated with the reduction in protoscolex and metacestode viability.Fil: Nicolao, María Celeste. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Denegri, Guillermo Maria. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cárcamo, Juan Guillermo. Universidad Austral de Chile.; ChileFil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; ArgentinaElsevier Ireland2014-02info: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/11336/25778Nicolao, María Celeste; Denegri, Guillermo Maria; Cárcamo, Juan Guillermo; Cumino, Andrea Carina; P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus; Elsevier Ireland; Parasitology International; 63; 1; 2-2014; 1-81383-5769CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1383576913001591info:eu-repo/semantics/altIdentifier/doi/10.1016/j.parint.2013.09.017info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:59:55Zoai:ri.conicet.gov.ar:11336/25778instacron: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:34982025-09-29 09:59:55.333CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus
title P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus
spellingShingle P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus
Nicolao, María Celeste
Echinococcus Granulosus
Gene Expression
Glycoprotein P
title_short P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus
title_full P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus
title_fullStr P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus
title_full_unstemmed P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus
title_sort P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus
dc.creator.none.fl_str_mv Nicolao, María Celeste
Denegri, Guillermo Maria
Cárcamo, Juan Guillermo
Cumino, Andrea Carina
author Nicolao, María Celeste
author_facet Nicolao, María Celeste
Denegri, Guillermo Maria
Cárcamo, Juan Guillermo
Cumino, Andrea Carina
author_role author
author2 Denegri, Guillermo Maria
Cárcamo, Juan Guillermo
Cumino, Andrea Carina
author2_role author
author
author
dc.subject.none.fl_str_mv Echinococcus Granulosus
Gene Expression
Glycoprotein P
topic Echinococcus Granulosus
Gene Expression
Glycoprotein P
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv P-glycoprotein (Pgp) is an ATP-dependent transporter involved in the efflux of a wide variety of lipophilic substrates, such as toxins and xenobiotics, out of cells. Pgp expression level is associated with the ineffective therapeutic treatment of cancer cells and microbial pathogens which gives it high clinical importance. Research on these transporters in helminths is limited. This work describes for the first time the Echinococcus granulosus Pgp (Eg-Pgp) expression, in a model cestode parasite and an important human pathogen. Based on calcein efflux assays in the presence of common Pgp modulators, we demonstrated the occurrence of active Eg-Pgp in protoscoleces and metacestodes. Eg-Pgp, which showed a molecular mass of ~130 kDa in western blots, is localized in the suckers and the tegument of control protoscoleces as well as in the subtegument or all parenchymatous cells of protoscoleces treated with Pgp-interfering agents. We also identified five genes encoding Pgp which are constitutively expressed in protoscoleces and metacestodes. We showed that the Eg-pgp1 and Eg-pgp2 transcripts were up-regulated in response to in vitro drug treatment with amiodarone and loperamide, in agreement with the increased polypeptide levels. Finally, in vitro treatment of protoscoleces and metacestodes with trifluoperazine and loperamide was lethal to the parasites. This indicates that both drugs as well as cyclosporine A negatively modulate the E. granulosus Pgp efflux activity, favoring the retention of these drugs in the larval tissue. These events could be associated with the reduction in protoscolex and metacestode viability.
Fil: Nicolao, María Celeste. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Denegri, Guillermo Maria. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Cárcamo, Juan Guillermo. Universidad Austral de Chile.; Chile
Fil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Biologia. Laboratorio de Zoonosis Parasitarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Departamento de Química; Argentina
description P-glycoprotein (Pgp) is an ATP-dependent transporter involved in the efflux of a wide variety of lipophilic substrates, such as toxins and xenobiotics, out of cells. Pgp expression level is associated with the ineffective therapeutic treatment of cancer cells and microbial pathogens which gives it high clinical importance. Research on these transporters in helminths is limited. This work describes for the first time the Echinococcus granulosus Pgp (Eg-Pgp) expression, in a model cestode parasite and an important human pathogen. Based on calcein efflux assays in the presence of common Pgp modulators, we demonstrated the occurrence of active Eg-Pgp in protoscoleces and metacestodes. Eg-Pgp, which showed a molecular mass of ~130 kDa in western blots, is localized in the suckers and the tegument of control protoscoleces as well as in the subtegument or all parenchymatous cells of protoscoleces treated with Pgp-interfering agents. We also identified five genes encoding Pgp which are constitutively expressed in protoscoleces and metacestodes. We showed that the Eg-pgp1 and Eg-pgp2 transcripts were up-regulated in response to in vitro drug treatment with amiodarone and loperamide, in agreement with the increased polypeptide levels. Finally, in vitro treatment of protoscoleces and metacestodes with trifluoperazine and loperamide was lethal to the parasites. This indicates that both drugs as well as cyclosporine A negatively modulate the E. granulosus Pgp efflux activity, favoring the retention of these drugs in the larval tissue. These events could be associated with the reduction in protoscolex and metacestode viability.
publishDate 2014
dc.date.none.fl_str_mv 2014-02
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/11336/25778
Nicolao, María Celeste; Denegri, Guillermo Maria; Cárcamo, Juan Guillermo; Cumino, Andrea Carina; P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus; Elsevier Ireland; Parasitology International; 63; 1; 2-2014; 1-8
1383-5769
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25778
identifier_str_mv Nicolao, María Celeste; Denegri, Guillermo Maria; Cárcamo, Juan Guillermo; Cumino, Andrea Carina; P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus; Elsevier Ireland; Parasitology International; 63; 1; 2-2014; 1-8
1383-5769
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1383576913001591
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.parint.2013.09.017
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Ireland
publisher.none.fl_str_mv Elsevier Ireland
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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score 13.070432

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