Galectin-8 Induces Apoptosis in Jurkat T Cells by Phosphatidic Acid-mediated ERK1/2 Activation Supported by Protein Kinase A Down-regulation
dc.contributor.author | Norambuena, Andres | |
dc.contributor.author | Metz, Claudia | |
dc.contributor.author | Vicuna, Lucas | |
dc.contributor.author | Silva, Antonia | |
dc.contributor.author | Pardo, Evelyn | |
dc.contributor.author | Oyanadel, Claudia | |
dc.contributor.author | Massardo, Loreto | |
dc.contributor.author | Gonzalez, Alfonso | |
dc.contributor.author | Soza, Andrea | |
dc.date.accessioned | 2024-01-10T13:13:14Z | |
dc.date.available | 2024-01-10T13:13:14Z | |
dc.date.issued | 2009 | |
dc.description.abstract | Galectins 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.funder | Fondo Nacional de Desarrollo CientIfico y Tecnologico | |
dc.description.funder | Fondo Nacional de Areas Prioritarias | |
dc.description.funder | Financiamiento Basal para Centros Cientificos y Tecnologicos de Excelencia | |
dc.description.funder | Ministerio de Planificacion y Cooperacion de Chile | |
dc.fechaingreso.objetodigital | 2024-04-25 | |
dc.format.extent | 10 páginas | |
dc.fuente.origen | WOS | |
dc.identifier.doi | 10.1074/jbc.M808949200 | |
dc.identifier.eissn | 1083-351X | |
dc.identifier.pubmedid | MEDLINE:19276072 | |
dc.identifier.uri | https://doi.org/10.1074/jbc.M808949200 | |
dc.identifier.uri | https://repositorio.uc.cl/handle/11534/78283 | |
dc.identifier.wosid | WOS:000265688300011 | |
dc.information.autoruc | Medicina;Gonzalez A ;S/I;52306 | |
dc.information.autoruc | Medicina;Massardo L ;S/I;100068 | |
dc.information.autoruc | Medicina;Metz C;S/I;65286 | |
dc.information.autoruc | Agronomía e Ing. Forestal;Norambuena A ;S/I;94539 | |
dc.information.autoruc | Ciencias Biológicas;Pardo E;S/I;13491 | |
dc.information.autoruc | Ciencias Biológicas;Silva A ;S/I;3863 | |
dc.information.autoruc | Medicina;Soza A;S/I;129570 | |
dc.information.autoruc | Ciencias Biológicas;Vicuña L;S/I;126655 | |
dc.issue.numero | 19 | |
dc.language.iso | en | |
dc.nota.acceso | contenido completo | |
dc.pagina.final | 12679 | |
dc.pagina.inicio | 12670 | |
dc.publisher | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | |
dc.revista | JOURNAL OF BIOLOGICAL CHEMISTRY | |
dc.rights | acceso abierto | |
dc.subject | CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE | |
dc.subject | SYSTEMIC-LUPUS-ERYTHEMATOSUS | |
dc.subject | PHOSPHOLIPASE-D ACTIVITY | |
dc.subject | GROWTH-FACTOR RECEPTOR | |
dc.subject | DEPENDENT KINASE | |
dc.subject | MAP KINASE | |
dc.subject | CYTOKINE SECRETION | |
dc.subject | MAPK/ERK PATHWAY | |
dc.subject | PLASMA-MEMBRANE | |
dc.subject | IMMUNE-RESPONSE | |
dc.subject.ods | 03 Good Health and Well-being | |
dc.subject.odspa | 03 Salud y bienestar | |
dc.title | Galectin-8 Induces Apoptosis in Jurkat T Cells by Phosphatidic Acid-mediated ERK1/2 Activation Supported by Protein Kinase A Down-regulation | |
dc.type | artículo | |
dc.volumen | 284 | |
sipa.codpersvinculados | 52306 | |
sipa.codpersvinculados | 100068 | |
sipa.codpersvinculados | 65286 | |
sipa.codpersvinculados | 94539 | |
sipa.codpersvinculados | 13491 | |
sipa.codpersvinculados | 3863 | |
sipa.codpersvinculados | 129570 | |
sipa.codpersvinculados | 126655 | |
sipa.index | WOS | |
sipa.index | Scopus | |
sipa.trazabilidad | Carga SIPA;09-01-2024 |
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