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10.1152/ajpcell.00029.2014

http://scihub22266oqcxt.onion/10.1152/ajpcell.00029.2014
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C4233262!4233262!25231106
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suck abstract from ncbi


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pmid25231106      Am+J+Physiol+Cell+Physiol 2014 ; 307 (10): C920-7
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  • Sphingosine kinase 1 (Sphk1) negatively regulates platelet activation and thrombus formation #MMPMID25231106
  • Münzer P; Schmid E; Walker B; Fotinos A; Chatterjee M; Rath D; Vogel S; Hoffmann SM; Metzger K; Seizer P; Geisler T; Gawaz M; Borst O; Lang F
  • Am J Physiol Cell Physiol 2014[Nov]; 307 (10): C920-7 PMID25231106show ga
  • 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. Activation-dependent platelet integrin ?IIb?3 activation and secretion of platelets lacking functional sphingosine kinase 1 (sphk1?/?) and of wild-type platelets (sphk1+/+) 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 ?IIb?3 activation, and aggregation were all significantly increased in sphk1?/? platelets compared with sphk1+/+ 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 sphk1?/? mice. In conclusion, sphingosine kinase 1 is a powerful negative regulator of platelet function counteracting degranulation, aggregation, and thrombus formation.
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