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- W2325499644 abstract "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 α IIb β 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 Ca 2+ activity ([Ca 2+ ] 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 [Ca 2+ ] i , degranulation (release of alpha and dense granules), integrin α IIb β 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." @default.
- W2325499644 created "2016-06-24" @default.
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- W2325499644 date "2014-11-15" @default.
- W2325499644 modified "2023-10-17" @default.
- W2325499644 title "Sphingosine kinase 1 (Sphk1) negatively regulates platelet activation and thrombus formation" @default.
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- W2325499644 doi "https://doi.org/10.1152/ajpcell.00029.2014" @default.
- W2325499644 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4233262" @default.
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