Autor: |
Münzer, Patrick, Schmid, Evi, Walker, Britta, Fotinos, Anna, Chatterjee, Madhumita, Rath, Dominik, Vogel, Sebastian, Hoffmann, Sascha M., Metzger, Katja, Seizer, Peter, Geisler, Tobias, Gawaz, Meinrad, Borst, Oliver, Lang, Florian |
Předmět: |
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Zdroj: |
American Journal of Physiology: Cell Physiology; 11/15/2014, Vol. 307 Issue 10, pC920-C927, 8p |
Abstrakt: |
Sphingosine 1-phosphate (S1P) is a powerful regulator of platelet formation. Enzymes generating S1P include sphingosine kinase 1. The present study thus explored the role of sphingosine kinase 1 in platelet formation and function. Activationdependent platelet integrin αIIbβ3 activation and secretion of platelets lacking functional sphingosine kinase 1 (sphkl-/- and of wild-type platelets (sphkl+/+) were determined utilizing flow cytometry and chronolume luciferin assay. Cytosolic Ca2+ activity ([Ca2+]i) and aggregation were measured using fura-2 fluorescence and aggregometry, respectively. In vitro platelet adhesion and thrombus formation were evaluated using a flow chamber with shear rates of 1,700 s-1. Activation-dependent increase of [Ca2+]i, degranulation (release of alpha and dense granules), integrin αIIbβ3 activation, and aggregation were all significantly increased in sphkl platelets compared with sphkl+/+platelets. Moreover, while platelet adhesion and thrombus formation under arterial shear rates were significantly augmented in Sphk1-deficient platelets, bleeding time and blood count were unaffected in sphkl-/- mice. In conclusion, sphingosine kinase 1 is a powerful negative regulator of platelet function counteracting degranulation, aggregation, and thrombus formation. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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