Browsing by Author "Oyanadel, Claudia"

Now showing 1 - 9 of 9
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    AP1B sorts basolateral proteins in recycling and biosynthetic routes of MDCK cells
    (NATL ACAD SCIENCES, 2007) Gravotta, Diego; Deora, Ami; Perret, Emilie; Oyanadel, Claudia; Soza, Andrea; Schreiner, Ryan; Rodriguez Boulan, Enrique
    The epithelial-specific adaptor AP1B sorts basolateral proteins, but the trafficking routes where it performs its sorting role remain controversial. Here, we used an RNAi approach to knock down the medium subunit of AP1B (mu 1B) in the prototype epithelial cell line Madin-Darby canine kidney (MDCK). mu 1B-knocked down MDCK cells displayed loss of polarity of several endogenous and exogenous basolateral markers transduced via adenovirus vectors, but exhibited normal polarity of apical markers. We chose two well characterized basolateral protein markers, the transferrin receptor (TfR) and the vesicular stomatitis virus G protein, to study the sorting role of AP1B. A surface-capture assay introduced here showed that mu 1B-knocked down MDCK cells plated on filters at confluency and cultured for 4.5 d, sorted TfR correctly in the biosynthetic route but incorrectly in the recycling route. In contrast, these same cells missorted vesicular stomatitis virus G apically in the biosynthetic route. Strikingly, recently confluent MDCK cells (1-3 d) displayed AP1B-dependence in the biosynthetic route of TfR, which decreased with additional days in culture. Sucrose density gradient analysis detected AP1B predominantly in TfR-rich endosomal fractions in MDCK cells confluent for 1 and 4 d. Our results are consistent with the following model: AP1B sorts basolateral proteins in both biosynthetic and recycling routes of MDCK cells, as a result of its predominant functional localization in recycling endosomes, which constitute a post-Golgi station in the biosynthetic route of some plasma membrane proteins. TfR utilizes a direct route from Golgi to basolateral membrane that is established as the epithelial monolayer matures.
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    Epidermal growth factor receptor endocytic traffic perturbation by phosphatidate phosphohydrolase inhibition : new strategy against cancer
    (2014) Shaughnessy, Ronan Patrick; Retamal, Claudio; Oyanadel, Claudia; Norambuena Pérez, Andrés; López, Alejandro; Bravo Zehnder, Marcela; Montecino, Fabián, J.; Metz Baer, Claudia Andrea; Soza Gajardo, Andrea; González de la Rosa, Alfonso
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    Galectin-8 as an immunosuppressor in experimental autoimmune encephalomyelitis and a target of human early prognostic antibodies in multiple sclerosis
    (2017) Pardo, Evelyn; Cárcamo, Claudia; Uribe-San Martín, Reinaldo; Ciampi, Ethel; Segovia-Miranda, Fabián; Curkovic-Peña, Cristobal; Montecino, Fabián; Holmes, Christopher; Tichauer, Juan Enrique; Acuña, Eric; Osorio-Barrios, Francisco; Castro, Marjorie; Cortes, Priscilla; Oyanadel, Claudia; Valenzuela, David M.; Pacheco, Rodrigo; Naves, Rodrigo; Soza, Andrea; González, Alfonso
    Galectin-8 (Gal-8) is a member of a glycan-binding protein family that regulates the immune system, among other functions, and is a target of antibodies in autoimmune disorders. However, its role in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system (CNS), remains unknown. We study the consequences of Gal-8 silencing on lymphocyte subpopulations and the development of experimental autoimmune encephalitis (EAE), to then assess the presence and clinical meaning of anti-Gal-8 antibodies in MS patients. Lgals8/Lac-Z knock-in mice lacking Gal-8 expression have higher polarization toward Th17 cells accompanied with decreased CCR6+ and higher CXCR3+ regulatory T cells (Tregs) frequency. These conditions result in exacerbated MOG35-55 peptide-induced EAE. Gal-8 eliminates activated Th17 but not Th1 cells by apoptosis and ameliorates EAE in C57BL/6 wild-type mice. β-gal histochemistry reflecting the activity of the Gal-8 promoter revealed Gal-8 expression in a wide range of CNS regions, including high expression in the choroid-plexus. Accordingly, we detected Gal-8 in human cerebrospinal fluid, suggesting a role in the CNS immune-surveillance circuit. In addition, we show that MS patients generate function-blocking anti-Gal-8 antibodies with pathogenic potential. Such antibodies block cell adhesion and Gal-8-induced Th17 apoptosis. Furthermore, circulating anti-Gal-8 antibodies associate with relapsing-remitting MS (RRMS), and not with progressive MS phenotypes, predicting clinical disability at diagnosis within the first year of follow-up. Our results reveal that Gal-8 has an immunosuppressive protective role against autoimmune CNS inflammation, modulating the balance of Th17 and Th1 polarization and their respective Tregs. Such a role can be counteracted during RRMS by anti-Gal-8 antibodies, worsening disease prognosis. Even though anti-Gal-8 antibodies are not specific for MS, our results suggest that they could be a potential early severity biomarker in RRMS.
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    Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients
    (2013) Vicuña, Lucas; Pardo, Evelyn; Curkovic, Cristóbal; Doger, Remziye; Oyanadel, Claudia; Metz Baer, Claudia Andrea; Massardo Vega, Loreto; González de la Rosa, Alfonso; Soza Gajardo, Andrea
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    Galectin-8 Favors the Presentation of Surface-Tethered Antigens by Stabilizing the B Cell Immune Synapse
    (2018) Obino, Dorian; Fetler, Luc; Soza Gajardo, Andrea; Malbec, Odile; Saez, Jose; Labarca, Mariana; Oyanadel, Claudia; Del Valle Batalla, Felipe; Goles, Nicolas; Chikina, Aleksandra; Lankar, Danielle; Yuseff Sepúlveda, María Isabel; Segovia Miranda, Fabián Josué; Garcia, Camille; Léger, Thibaut; Gonzalez, Alfonso; Espéli, Marion; Lennon-Duménil, Ana-Maria
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    Galectin-8 Induces Apoptosis in Jurkat T Cells by Phosphatidic Acid-mediated ERK1/2 Activation Supported by Protein Kinase A Down-regulation
    (AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2009) Norambuena, Andres; Metz, Claudia; Vicuna, Lucas; Silva, Antonia; Pardo, Evelyn; Oyanadel, Claudia; Massardo, Loreto; Gonzalez, Alfonso; Soza, Andrea
    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.
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    Galectin-8 induces partial epithelial–mesenchymal transition with invasive tumorigenic capabilities involving a FAK/EGFR/proteasome pathway in Madin–Darby canine kidney cells
    (2018) Oyanadel, Claudia; Holmes Videla, Christopher Edward; Pardo Huguet, Evelyn Cristina; Retamal Villarroel, Claudio Enrique; Shaughnessy, Ronan Patrick; Smith, Patricio C.; Cortés Martínez, Priscilla Rocío; Bravo Zehnder, Marcela; Metz Baer, Claudia Andrea; Feuerhake, Teo; Romero, Diego; Roa Strauch, Juan Carlos Enrique; Montecinos, Viviana; Soza Gajardo, Andrea; González, Alfonso
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    Galectin-8 mediates fibrogenesis induced by cyclosporine in human gingival fibroblasts
    (2020) Patricio C. Smith; Metz Baer, Claudia Andrea; Peña, Adely de la; Oyanadel, Claudia; Ávila, Patricio; Arancibia, Rodrigo; Vicuña, Lucas; Retamal Villarroel, Claudio Enrique; Barake Sabbagh, M. Francisca; González de la Rosa, Alfonso; Soza Gajardo, Andrea
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    Resistance of leukemia cells to cytarabine chemotherapy is mediated by bone marrow stroma, involves cell-surface equilibrative nucleoside transporter-1 removal and correlates with patient outcome
    (2017) Macanas Pirard, Patricia; Broekhuizen, Richard; González, Alfonso; Oyanadel, Claudia; Ernst Diaz, Daniel Matias; García Cañete, Patricia; Montecinos Acuña, Viviana; Court G., Felipe; Ocqueteau Tachini, Mauricio; Ramírez Villanueva, Pablo Antonio; Nervi, Bruno