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Convergencia de vías de señalización en un modelo de apoptosis

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dc.contributor.advisorMatheus Merino, Luisa Marina
dc.creatorArarat Sarria, Monica
dc.creator.degreeMagíster en Ciencias con Énfasis en Genética Humana
dc.date.accessioned2014-08-12T12:57:57Z
dc.date.available2014-08-12T12:57:57Z
dc.date.created2014-06-20
dc.date.issued2014
dc.descriptionLa sepsis es un evento inflamatorio generalizado del organismo inducido por un daño causado generalmente por un agente infeccioso. El patógeno más frecuentemente asociado con esta entidad es el Staphylococcus aureus, responsable de la inducción de apoptosis en células endoteliales debida a la producción de ceramida. Se ha descrito el efecto protector de la proteína C activada (PCA) en sepsis y su relación con la disminución de la apoptosis de las células endoteliales. En este trabajo se analizó la activación de las quinasas AKT, ASK1, SAPK/JNK y p38 en un modelo de apoptosis endotelial usando las técnicas de Western Blotting y ELISA. Las células endoteliales (EA.hy926), se trataron con C2-ceramida (130μM) en presencia de inhibidores químicos de cada una de estas quinasas y PCA. La supervivencia de las células en presencia de inhibidores químicos y PCA fue evaluada por medio de ensayos de activación de las caspasas 3, 7 y 9, que verificaban la muerte celular por apoptosis. Los resultados evidencian que la ceramida reduce la activación de AKT y aumenta la activación de las quinasas ASK, SAPK/JNK y p38, en tanto que PCA ejerce el efecto contrario. Adicionalmente se encontró que la tiorredoxina incrementa la activación/fosforilación de AKT, mientras que la quinasa p38 induce la defosforilación de AKT.spa
dc.description.abstractSepsis is a generalized inflammatory event induced by the damage produced by an infectious agent. The pathogen most commonly associated with sepsis is Staphylococcus aureus, responsible for the induction of apoptosis in endothelial cells due to the production of ceramide. It has been previously described the protective effect of activated protein C (APC) in sepsis and its relation to the reduced apoptosis of endothelial cells. In this work, the activation of AKT, ASK1, SAPK / JNK and p38 kinase, in a model of endothelial apoptosis, was analyzed using the techniques of Western Blotting and ELISA. Endothelial cells (EA.hy926), were treated with C2-ceramide (130μM) in the presence of chemical inhibitors of each of these kinases and PCA. The survival of the cells in the presence of chemical and PCA inhibitors was evaluated by fluorescent assays of the activation of caspases 3, 7 and 9. The results showed that the ceramide reduced AKT activation and increases activation of ASK, SAPK / JNK and p38 kinases, whereas PCA exerts the opposite effect. Additionally, it was found that the thioredoxin increases the activation / phosphorylation of AKT, whereas p38 kinase induces AKT dephosphorylation.eng
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dc.identifier.doihttps://doi.org/10.48713/10336_8782
dc.identifier.urihttp://repository.urosario.edu.co/handle/10336/8782
dc.language.isospa
dc.publisherUniversidad del Rosariospa
dc.publisher.departmentFacultad de medicinaspa
dc.publisher.programMaestría en Ciencias con Énfasis en Genética Humanaspa
dc.rights.accesRightsinfo:eu-repo/semantics/openAccess
dc.rights.accesoAbierto (Texto Completo)spa
dc.rights.ccAtribución-NoComercial-SinDerivadas 2.5 Colombiaspa
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dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/2.5/co/
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dc.source.instnameinstname:Universidad del Rosariospa
dc.source.reponamereponame:Repositorio Institucional EdocURspa
dc.subjectapoptosisspa
dc.subjectsepsisspa
dc.subjectendoteliospa
dc.subjectPCAspa
dc.subjectAKTspa
dc.subjectJNKspa
dc.subjectASKspa
dc.subjectp38spa
dc.subjectceramidaspa
dc.subjectmuerte celularspa
dc.subject.ddcCiencias médicas, Medicina
dc.subject.decsApoptosisspa
dc.subject.decsAsepsiaspa
dc.subject.decsMuerte celularspa
dc.subject.decsGenéticaspa
dc.subject.keywordapoptosiseng
dc.subject.keywordceramideeng
dc.subject.keywordAPCeng
dc.subject.keywordp38eng
dc.subject.keywordJNKeng
dc.subject.keywordAKTeng
dc.subject.keywordASKeng
dc.subject.keywordcell deatheng
dc.titleConvergencia de vías de señalización en un modelo de apoptosisspa
dc.typemasterThesiseng
dc.type.hasVersioninfo:eu-repo/semantics/submittedVersion
dc.type.spaTesis de maestríaspa
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Maestría en Genética Humana