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dc.creatorNorambuena ,A.
dc.creatorMetz C.
dc.creatorVicuña L.
dc.creatorSilva A.
dc.creatorPardo E.
dc.creatorOyanadel C.
dc.creatorGonzález A.
dc.creatorSoza A
dc.date.accessioned2019-12-18T18:15:01Z
dc.date.available2019-12-18T18:15:01Z
dc.date.issued2009
dc.identifier.urihttp://hdl.handle.net/10533/237215
dc.description.abstractGalectins have been implicated in T cell homeostasis playing complementary pro-apoptotic roles. Here we show that galectin-8 (Gal-8) is a potent pro-apoptotic agent in Jurkat T cells inducing a complex phospholipase D/phosphatidic acid signaling pathway that has not been reported for any galectin before. Gal-8 increases phosphatidic signaling, which enhances the activity of both ERK1/2 and type 4 phosphodiesterases (PDE4), with a subsequent decrease in basal protein kinase A activity. Strikingly, rolipram inhibition of PDE4 decreases ERK1/2 activity. Thus Gal-8-induced PDE4 activation releases a negative influence of cAMP/protein kinase A on ERK1/2. The resulting strong ERK1/2 activation leads to expression of the death factor Fas ligand and caspase-mediated apoptosis. Several conditions that decrease ERK1/2 activity also decrease apoptosis, such as anti-Fas ligand blocking antibodies. In addition, experiments with freshly isolated human peripheral blood mononuclear cells, previously stimulated with anti-CD3 and anti-CD28, show that Gal-8 is pro-apoptotic on activated T cells, most likely on a subpopulation of them. Anti-Gal-8 autoantibodies from patients with systemic lupus erythematosus block the apoptotic effect of Gal-8. These results implicate Gal-8 as a novel T cell suppressive factor, which can be counterbalanced by function-blocking autoantibodies in autoimmunity.
dc.language.isoeng
dc.relationinstname: Conicyt
dc.relationreponame: Repositorio Digital RI2.0
dc.relation.urihttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2675996/
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.titleGalectin-8 Induces Apoptosis in Jurkat T Cells by Phosphatidic Acid-mediated ERK1/2 Activation Supported by Protein Kinase A Down-regulation
dc.typeArticulo
dc.identifier.folio13980001
dc.relation.projectidinfo:eu-repo/grantAgreement/Fondap/13980001
dc.rights.driverinfo:eu-repo/semantics/openAccess
dc.title.journalJ Biol Chem
dc.type.driverinfo:eu-repo/semantics/article
dc.description.shortconicytprogramFONDAP
dc.description.shortconicytprogramFONDAP
dc.type.openaireinfo:eu-repo/semantics/publishedVersion


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