Browsing by Author "Zamorano, Patricia"

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    Galectin-8 induces endothelial hyperpermeability through the eNOS pathway involving S-nitrosylation-mediated adherens junction disassembly
    (2019) Zamorano, Patricia; Koning, Tania; Oyanadel, Claudia; Mardones, Gonzalo A.; Ehrenfeld, Pamela; Boric, Mauricio P.; Gonzalez, Alfonso; Soza, Andrea; Sanchez, Fabiola A.
    The permeability of endothelial cells is regulated by the stability of the adherens junctions, which is highly sensitive to kinase-mediated phosphorylation and endothelial nitric oxide synthase (eNOS)-mediated S-nitrosylation of its protein components. Solid tumors can produce a variety of factors that stimulate these signaling pathways leading to endothelial cell hyperpermeability. This generates stromal conditions that facilitate tumoral growth and dissemination. Galectin-8 (Gal-8) is overexpressed in several carcinomas and has a variety of cellular effects that can contribute to tumor pathogenicity, including angiogenesis. Here we explored whether Gal-8 has also a role in endothelial permeability. We show that recombinant Gal-8 activates eNOS, induces S-nitrosylation of p120-catenin (p120) and dissociation of adherens junction, leading to hyperpermeability of the human endothelial cell line EAhy926. This pathway involves focal-adhesion kinase (FAK) activation downstream of eNOS as a requirement for eNOS-mediated p120 S-nitrosylation. This suggests a reciprocal, yet little understood, regulation of phosphorylation and S-nitrosylation events acting upon adherens junction permeability. In addition, glutathione S-transferase (GST)-Gal-8 pull-down experiments and function-blocking beta 1-integrin antibodies point to beta 1-integrins as cell surface components involved in Gal-8-induced hyperpermeability. Endogenous Gal-8 secreted from the breast cancer cell line MCF-7 has similar hyperpermeability and signaling effects. Furthermore, the mouse cremaster model system showed that Gal-8 also activates eNOS, induces S-nitrosylation of adherens junction components and is an effective hyperpermeability agent in vivo. These results add endothelial permeability regulation by S-nitrosylation as a new function of Gal-8 that can potentially contribute to the pathogenicity of tumors overexpressing this lectin.
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    S-Nitrosation of β-Catenin and p120 Catenin A Novel Regulatory Mechanism in Endothelial Hyperpermeability
    (2012) Marin, Natalie; Zamorano, Patricia; Carrasco, Rodrigo; Mujica, Patricio; Gonzalez, Francisco G.; Quezada, Claudia; Meininger, Cynthia J.; Boric, Mauricio P.; Duran, Walter N.; Sanchez, Fabiola A.
    Rationale: Endothelial adherens junction proteins constitute an important element in the control of microvascular permeability. Platelet-activating factor (PAF) increases permeability to macromolecules via translocation of endothelial nitric oxide synthase (eNOS) to cytosol and stimulation of eNOS-derived nitric oxide signaling cascade. The mechanisms by which nitric oxide signaling regulates permeability at adherens junctions are still incompletely understood.
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    S-nitrosylation of VASP at Cysteine 64 Mediates Inflammation Stimulated Increase in Microvascular Permeability
    (2017) Zamorano, Patricia; Marín, Natalie; Córdova, Francisco; Aguilar, Alejandra; Meininger, Cynthia; Boric P., Mauricio; Golenhofen, Nikola; Contreras, Jorge; Sarmiento, José; Durán, Walter N.; Sánchez, Fabiola A.
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    S-nitrosylation regulates VE-cadherin phosphorylation and internalization in microvascular permeability
    (2016) Guequén, Anita; Carrasco, Rodrigo; Zamorano, Patricia; Rebolledo, Lorena; Burboa, Pía; Sarmiento, José; Boric P., Mauricio; Korayem, Adam; Durán, Walter N.; Sánchez, Fabiola A.