دورية أكاديمية
Sphingosine 1-Phosphate Produced by Sphingosine Kinase 2 Intrinsically Controls Platelet Aggregation In Vitro and In Vivo
| العنوان: | Sphingosine 1-Phosphate Produced by Sphingosine Kinase 2 Intrinsically Controls Platelet Aggregation In Vitro and In Vivo |
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| المؤلفون: | Urtz, Nicole, Gaertner, Florian, von Bruehl, Marie-Luise, Chandraratne, Sue, Rahimi, Faridun, Zhang, Lingli, Orban, Mathias, Barocke, Verena, Beil, Johannes, Schubert, Irene, Lorenz, Michael, Legate, Kyle R, Huwiler, Andrea, Pfeilschifter, Josef M, Beerli, Christian, Ledieu, David, Persohn, Elke, Billich, Andreas, Baumruker, Thomas, Mederos y Schnitzler, Michael, Massberg, Steffen |
| المصدر: | Urtz, Nicole; Gaertner, Florian; von Bruehl, Marie-Luise; Chandraratne, Sue; Rahimi, Faridun; Zhang, Lingli; Orban, Mathias; Barocke, Verena; Beil, Johannes; Schubert, Irene; Lorenz, Michael; Legate, Kyle R; Huwiler, Andrea; Pfeilschifter, Josef M; Beerli, Christian; Ledieu, David; Persohn, Elke; Billich, Andreas; Baumruker, Thomas; Mederos y Schnitzler, Michael; . (2015). Sphingosine 1-Phosphate Produced by Sphingosine Kinase 2 Intrinsically Controls Platelet Aggregation In Vitro and In Vivo. Circulation research, 117(4), pp. 376-387. Lippincott Williams & Wilkins 10.1161/CIRCRESAHA.115.306901 |
| بيانات النشر: | Lippincott Williams & Wilkins |
| سنة النشر: | 2015 |
| المجموعة: | BORIS (Bern Open Repository and Information System, University of Bern) |
| مصطلحات موضوعية: | 610 Medicine & health |
| الوصف: | RATIONALE Platelets are known to play a crucial role in hemostasis. Sphingosine kinases (Sphk) 1 and 2 catalyze the conversion of sphingosine to the bioactive metabolite sphingosine 1-phosphate (S1P). Although platelets are able to secrete S1P on activation, little is known about a potential intrinsic effect of S1P on platelet function. OBJECTIVE To investigate the role of Sphk1- and Sphk2-derived S1P in the regulation of platelet function. METHODS AND RESULTS We found a 100-fold reduction in intracellular S1P levels in platelets derived from Sphk2(-/-) mutants compared with Sphk1(-/-) or wild-type mice, as analyzed by mass spectrometry. Sphk2(-/-) platelets also failed to secrete S1P on stimulation. Blood from Sphk2-deficient mice showed decreased aggregation after protease-activated receptor 4-peptide and adenosine diphosphate stimulation in vitro, as assessed by whole blood impedance aggregometry. We revealed that S1P controls platelet aggregation via the sphingosine 1-phosphate receptor 1 through modulation of protease-activated receptor 4-peptide and adenosine diphosphate-induced platelet activation. Finally, we show by intravital microscopy that defective platelet aggregation in Sphk2-deficient mice translates into reduced arterial thrombus stability in vivo. CONCLUSIONS We demonstrate that Sphk2 is the major Sphk isoform responsible for the generation of S1P in platelets and plays a pivotal intrinsic role in the control of platelet activation. Correspondingly, Sphk2-deficient mice are protected from arterial thrombosis after vascular injury, but have normal bleeding times. Targeting this pathway could therefore present a new therapeutic strategy to prevent thrombosis. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://boris.unibe.ch/76762Test/ |
| الإتاحة: | https://doi.org/10.1161/CIRCRESAHA.115.306901Test https://boris.unibe.ch/76762/1/Sphingosine%201-Phosphate%20Produced%20by%20Sphingosine.pdfTest https://boris.unibe.ch/76762Test/ |
| حقوق: | info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.764B96C5 |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |