| Human platelets express and are activated by galectin-8. | |
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MedLine Citation:
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PMID: 20858220 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Gals (galectins) are proteins with glycan affinity that are emerging as mediators of atherosclerosis. Despite the similarities in structure and sequence, different Gals exert distinct effects on their target cells. We have shown that Gal-1 triggers platelet activation, suggesting a role for Gals in thrombus formation. Since Gal-8 is expressed upon endothelial activation and also contributes to inflammation, to understand further the role of these lectins in haemostasis, we evaluated the effect of Gal-8 on human platelets. Gal-8 bound specific glycans in the platelet membrane and triggered spreading, calcium mobilization and fibrinogen binding. It also promoted aggregation, thromboxane generation, P-selectin expression and granule secretion. GP (glycoprotein) αIIb and Ib-V were identified as putative Gal-8 counter-receptors by MS. Studies performed using platelets from Glanzmann's thromboasthenia and Bernard-Soulier syndrome patients confirmed that GPIb is essential for transducing Gal-8 signalling. Accordingly, Src, PLC2γ (phospholipase C2γ), ERK (extracellular-signal-regulated kinase) and PI3K (phosphoinositide 3-kinase)/Akt downstream molecules were involved in the Gal-8 signalling pathway. Gal-8 fragments containing either the N- or C-terminal carbohydrate-recognition domains showed that activation is exerted through the N-terminus. Western blotting and cytometry showed that platelets not only contain Gal-8, but also expose Gal-8 after thrombin activation. These findings reveal Gal-8 as a potent platelet activator, supporting a role for this lectin in thrombosis and inflammation. |
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Authors:
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Maria Albertina Romaniuk; Maria Virginia Tribulatti; Valentina Cattaneo; Maria Jose Lapponi; Felisa Concepcion Molinas; Oscar Campetella; Mirta Schattner |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Biochemical journal Volume: 432 ISSN: 1470-8728 ISO Abbreviation: Biochem. J. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-26 Completed Date: 2011-01-06 Revised Date: 2011-09-06 |
Medline Journal Info:
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Nlm Unique ID: 2984726R Medline TA: Biochem J Country: England |
Other Details:
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Languages: eng Pagination: 535-47 Citation Subset: IM |
Affiliation:
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Thrombosis I Laboratory, Hematological Research Institute, National Academy of Medicine, CONICET, Buenos Aires, Argentina. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bernard-Soulier Syndrome / metabolism Blood Platelets / drug effects, physiology*, secretion Calcium Signaling Cell Membrane / metabolism Galectins / chemistry, genetics, physiology* Humans Immobilized Proteins / metabolism Integrin alpha2 / metabolism Mice Peptide Fragments / metabolism Platelet Activation / drug effects, physiology* Platelet Glycoprotein GPIb-IX Complex / metabolism Protein Interaction Domains and Motifs Protein Isoforms / chemistry, genetics, metabolism Protein Transport Recombinant Proteins / chemistry, metabolism Secretory Vesicles / physiology Solubility Thrombasthenia / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Galectins; 0/ITGA2B protein, human; 0/Immobilized Proteins; 0/Integrin alpha2; 0/LGALS8 protein, human; 0/Peptide Fragments; 0/Platelet Glycoprotein GPIb-IX Complex; 0/Protein Isoforms; 0/Recombinant Proteins; 0/galectin-8, mouse |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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