Show simple item record

dc.contributor.author Arana, Maite Rocío
dc.contributor.author Tocchetti, Guillermo Nicolás
dc.contributor.author Domizi, Pablo Daniel
dc.contributor.author Arias, Agostina
dc.contributor.author Rigalli, Juan Pablo
dc.contributor.author Ruiz, Maria Laura
dc.contributor.author Luquita, Marcelo Gabriel
dc.contributor.author Banchio, Claudia Elena
dc.contributor.author Mottino, Aldo Domingo
dc.contributor.author Villanueva, Silvina Stella Maris
dc.date.available 2016-06-03T18:14:28Z
dc.date.issued 2015-07
dc.identifier.citation Arana, Maite Rocío; Tocchetti, Guillermo Nicolás; Domizi, Pablo Daniel; Arias, Agostina; Rigalli, Juan Pablo; et al.; Coordinated Induction of GST and MRP2 by cAMP in Caco-2 Cells. Role of protein kinase A signaling pathway and toxicological relevance; Elsevier; Toxicology and Applied Pharmacology; 287; 2; 7-2015; 178-190
dc.identifier.issn 0041-008X
dc.identifier.uri http://hdl.handle.net/11336/6033
dc.description.abstract The cAMP pathway is a universal signaling pathway regulating many cellular processes including metabolic routes, growth and differentiation. However, its effects on xenobiotic biotransformation and transport systems are poorly characterized. The effect of cAMP on expression and activity of GST and MRP2 was evaluated in Caco-2 cells, a model of intestinal epithelium. Cells incubated with the cAMP permeable analog dibutyryl cyclic AMP (db-cAMP: 1,10,100 μM) for 48 h exhibited a dose–response increase in GST class α and MRP2 protein expression. Incubation with forskolin, an activator of adenylyl cyclase, confirmed the association between intracellular cAMP and upregulation of MRP2. Consistent with increased expression of GSTα and MRP2, db-cAMP enhanced their activities, as well as cytoprotection against the common substrate 1-chloro-2,4-dinitrobenzene. Pretreatment with protein kinase A (PKA) inhibitors totally abolished upregulation of MRP2 and GSTα induced by db-cAMP. In silico analysis together with experiments consisting of treatment with db-cAMP of Caco-2 cells transfected with a reporter construct containing CRE and AP-1 sites evidenced participation of these sites in MRP2 upregulation. Further studies involving the transcription factors CREB and AP-1 (c-JUN, c-FOS and ATF2) demonstrated increased levels of total c-JUN and phosphorylation of c-JUN and ATF2 by db-cAMP, which were suppressed by a PKA inhibitor. Co-immunoprecipitation and ChIP assay studies demonstrated that db-cAMP increased c-JUN/ATF2 interaction, with further recruitment to the region of the MRP2 promoter containing CRE and AP-1 sites. We conclude that cAMP induces GSTα and MRP2 expression and activity in Caco-2 cells via the PKA pathway, thus regulating detoxification of specific xenobiotics.
dc.format application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.subject mrp2
dc.subject intestino
dc.subject AMPc
dc.subject transporte
dc.subject.classification Bioquímica y Biología Molecular
dc.subject.classification Ciencias Biológicas
dc.subject.classification CIENCIAS NATURALES Y EXACTAS
dc.title Coordinated Induction of GST and MRP2 by cAMP in Caco-2 Cells. Role of protein kinase A signaling pathway and toxicological relevance
dc.type info:eu-repo/semantics/article
dc.type info:ar-repo/semantics/artículo
dc.type info:eu-repo/semantics/publishedVersion
dc.date.updated 2016-06-01T13:48:44Z
dc.journal.volume 287
dc.journal.number 2
dc.journal.pagination 178-190
dc.journal.pais Países Bajos
dc.journal.ciudad Amsterdam
dc.description.fil Fil: Arana, Maite Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Tocchetti, Guillermo Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Domizi, Pablo Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
dc.description.fil Fil: Arias, Agostina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Rigalli, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Ruiz, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Luquita, Marcelo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Banchio, Claudia Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Biología Molecular y Celular de Rosario; Argentina
dc.description.fil Fil: Mottino, Aldo Domingo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.description.fil Fil: Villanueva, Silvina Stella Maris. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Rosario. Instituto de Fisiología Experimental (i); Argentina
dc.journal.title Toxicology and Applied Pharmacology
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/purl/http://www.sciencedirect.com/science/article/pii/S0041008X15300119
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1016/j.taap.2015.06.003
dc.relation.alternativeid info:eu-repo/semantics/altIdentifier/doi/10.1016/j.taap.2015.06.003


Archivos asociados

Icon
Blocked Acceso no disponible

This item appears in the following Collection(s)

  • Articulos(IBR) [322]
    Articulos de INST.DE BIOLOGIA MOLECULAR Y CELULAR DE ROSARIO
  • Articulos(IFISE) [100]
    Articulos de INST.DE FISIOLOGIA EXPERIMENTAL (I)

Show simple item record

info:eu-repo/semantics/restrictedAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Atribución-NoComercial-SinDerivadas 2.5 Argentina (CC BY-NC-ND 2.5 AR)