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dc.contributor.author
Nicolao, María Celeste
dc.contributor.author
Loos, Julia Alexandra
dc.contributor.author
Rodríguez Rodrígues, Christian Fernando Ariel
dc.contributor.author
Beas, Viviana
dc.contributor.author
Cumino, Andrea Carina
dc.date.available
2019-03-28T22:10:32Z
dc.date.issued
2017-08
dc.identifier.citation
Nicolao, María Celeste; Loos, Julia Alexandra; Rodríguez Rodrígues, Christian Fernando Ariel; Beas, Viviana; Cumino, Andrea Carina; Bortezomib initiates endoplasmic reticulum stress, elicits autophagy and death in echinococcus granulosus larval stage; Public Library of Science; Plos One; 12; 8; 8-2017; 1-19; e0181528
dc.identifier.issn
1932-6203
dc.identifier.uri
http://hdl.handle.net/11336/72778
dc.description.abstract
Cystic echinococcosis (CE) is a worldwide distributed helminthic zoonosis caused by Echinococcus granulosus. Benzimidazole derivatives are currently the only drugs for chemotherapeutic treatment of CE. However, their low efficacy and the adverse effects encourage the search for new therapeutic targets. We evaluated the in vitro efficacy of Bortezomib (Bz), a proteasome inhibitor, in the larval stage of the parasite. After 96 h, Bz showed potent deleterious effects at a concentration of 5 μM and 0.5 μM in protoscoleces and metacestodes, respectively (P < 0.05). After 48 h of exposure to this drug, it was triggered a mRNA overex-pression of chaperones (Eg-grp78 and Eg-calnexin) and of Eg-ire2/Eg-xbp1 (the conserved UPR pathway branch) in protoscoleces. No changes were detected in the transcriptional expression of chaperones in Bz-treated metacestodes, thus allowing ER stress to be evident and viability to highly decrease in comparison with protoscoleces. We also found that Bz treatment activated the autophagic process in both larval forms. These facts were evidenced by the increase in the amount of transcripts of the autophagy related genes (Eg-atg6, Eg-atg8, Eg-atg12, Eg-atg16) together with the increase in Eg-Atg8-II detected by western blot and by in toto immunofluorescence labeling. It was further confirmed by direct observation of autophagic structures by electronic microscopy. Finally, in order to determine the impact of autophagy induction on Echinococcus cell viability, we evaluated the efficacy of Bz in combination with rapamycin and a synergistic cytotoxic effect on protoscolex viability was observed when both drugs were used together. In conclusion, our findings demonstrated that Bz induced endoplasmic reticulum stress, autophagy and subsequent death allowing to identify unstudied parasite-host pathways that could provide a new insight for control of parasitic diseases.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
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
Bortezomib
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Endoplasmic Reticulum Stress
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Autophagy
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Otras Ciencias Biológicas
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Ciencias Biológicas
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CIENCIAS NATURALES Y EXACTAS
dc.title
Bortezomib initiates endoplasmic reticulum stress, elicits autophagy and death in echinococcus granulosus larval stage
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2019-03-27T14:50:50Z
dc.journal.volume
12
dc.journal.number
8
dc.journal.pagination
1-19; e0181528
dc.journal.pais
Estados Unidos
dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Nicolao, María Celeste. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Loos, Julia Alexandra. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Rodríguez Rodrígues, Christian Fernando Ariel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de Mar del Plata; Argentina
dc.description.fil
Fil: Beas, Viviana. Hospital Privado de Comunidad; Argentina. Universidad Nacional de Mar del Plata; Argentina
dc.description.fil
Fil: Cumino, Andrea Carina. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.journal.title
Plos One
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0181528
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0181528


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