Galectin-8 Induces Apoptosis in Jurkat T Cells by Phosphatidic Acid-mediated ERK1/2 Activation Supported by Protein Kinase A Down-regulation

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dc.contributor.authorNorambuena, Andres
dc.contributor.authorMetz, Claudia
dc.contributor.authorVicuna, Lucas
dc.contributor.authorSilva, Antonia
dc.contributor.authorPardo, Evelyn
dc.contributor.authorOyanadel, Claudia
dc.contributor.authorMassardo, Loreto
dc.contributor.authorGonzalez, Alfonso
dc.contributor.authorSoza, Andrea
dc.date.accessioned2024-01-10T13:13:14Z
dc.date.available2024-01-10T13:13:14Z
dc.date.issued2009
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.description.funderFondo Nacional de Desarrollo CientIfico y Tecnologico
dc.description.funderFondo Nacional de Areas Prioritarias
dc.description.funderFinanciamiento Basal para Centros Cientificos y Tecnologicos de Excelencia
dc.description.funderMinisterio de Planificacion y Cooperacion de Chile
dc.fechaingreso.objetodigital2024-04-25
dc.format.extent10 páginas
dc.fuente.origenWOS
dc.identifier.doi10.1074/jbc.M808949200
dc.identifier.eissn1083-351X
dc.identifier.pubmedidMEDLINE:19276072
dc.identifier.urihttps://doi.org/10.1074/jbc.M808949200
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/78283
dc.identifier.wosidWOS:000265688300011
dc.information.autorucMedicina;Gonzalez A ;S/I;52306
dc.information.autorucMedicina;Massardo L ;S/I;100068
dc.information.autorucMedicina;Metz C;S/I;65286
dc.information.autorucAgronomía e Ing. Forestal;Norambuena A ;S/I;94539
dc.information.autorucCiencias Biológicas;Pardo E;S/I;13491
dc.information.autorucCiencias Biológicas;Silva A ;S/I;3863
dc.information.autorucMedicina;Soza A;S/I;129570
dc.information.autorucCiencias Biológicas;Vicuña L;S/I;126655
dc.issue.numero19
dc.language.isoen
dc.nota.accesocontenido completo
dc.pagina.final12679
dc.pagina.inicio12670
dc.publisherAMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
dc.revistaJOURNAL OF BIOLOGICAL CHEMISTRY
dc.rightsacceso abierto
dc.subjectCYCLIC-NUCLEOTIDE PHOSPHODIESTERASE
dc.subjectSYSTEMIC-LUPUS-ERYTHEMATOSUS
dc.subjectPHOSPHOLIPASE-D ACTIVITY
dc.subjectGROWTH-FACTOR RECEPTOR
dc.subjectDEPENDENT KINASE
dc.subjectMAP KINASE
dc.subjectCYTOKINE SECRETION
dc.subjectMAPK/ERK PATHWAY
dc.subjectPLASMA-MEMBRANE
dc.subjectIMMUNE-RESPONSE
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleGalectin-8 Induces Apoptosis in Jurkat T Cells by Phosphatidic Acid-mediated ERK1/2 Activation Supported by Protein Kinase A Down-regulation
dc.typeartículo
dc.volumen284
sipa.codpersvinculados52306
sipa.codpersvinculados100068
sipa.codpersvinculados65286
sipa.codpersvinculados94539
sipa.codpersvinculados13491
sipa.codpersvinculados3863
sipa.codpersvinculados129570
sipa.codpersvinculados126655
sipa.indexWOS
sipa.indexScopus
sipa.trazabilidadCarga SIPA;09-01-2024
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