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dc.contributor.author
Nicolao, María Celeste
dc.contributor.author
Denegri, Guillermo Maria
dc.contributor.author
Cárcamo, Juan Guillermo
dc.contributor.author
Cumino, Andrea Carina
dc.date.available
2017-10-03T17:12:01Z
dc.date.issued
2014-02
dc.identifier.citation
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
dc.identifier.issn
1383-5769
dc.identifier.uri
http://hdl.handle.net/11336/25778
dc.description.abstract
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.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Elsevier Ireland
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
Echinococcus Granulosus
dc.subject
Gene Expression
dc.subject
Glycoprotein P
dc.subject.classification
Bioquímica y Biología Molecular
dc.subject.classification
Ciencias Biológicas
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
dc.title
P-glycoprotein expression and pharmacological modulation in larval stages of Echinococcus granulosus
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2017-09-29T14:45:57Z
dc.journal.volume
63
dc.journal.number
1
dc.journal.pagination
1-8
dc.journal.pais
Irlanda
dc.journal.ciudad
Shannon
dc.description.fil
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
dc.description.fil
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
dc.description.fil
Fil: Cárcamo, Juan Guillermo. Universidad Austral de Chile.; Chile
dc.description.fil
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
dc.journal.title
Parasitology International
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/http://www.sciencedirect.com/science/article/pii/S1383576913001591
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.parint.2013.09.017
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