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10.1016/j.bbalip.2014.08.013

http://scihub22266oqcxt.onion/10.1016/j.bbalip.2014.08.013
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C4223867!4223867!25158625
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suck abstract from ncbi


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pmid25158625      Biochim+Biophys+Acta 2014 ; 1841 (11): 1581-9
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  • Granule-Mediated Release of Sphingosine-1-Phosphate by Activated Platelets* #MMPMID25158625
  • Jonnalagadda D; Sunkara M; Morris AJ; Whiteheart SW
  • Biochim Biophys Acta 2014[Nov]; 1841 (11): 1581-9 PMID25158625show ga
  • Sphingosine-1-phosphate (S1P) is an intracellularly generated bioactive lipid essential for development, vascular integrity, and immunity. These functions are mediated by S1P-selective cell surface G-protein coupled receptors. S1P signaling therefore requires extracellular release of this lipid. Several cell types release S1P and evidence for both plasma membrane transporter-mediated and vesicle-dependent secretion has been presented. Platelets are an important source of S1P and can release it in response to agonists generated at sites of vascular injury. S1P release from agonist-stimulated platelets was measured in the presence of a carrier molecule (albumin) using HPLCMS/MS. The kinetics and agonist-dependence of S1P release were similar to that of other granule cargo e.g. platelet factor IV (PF4). Agonist-stimulated S1P release was defective in platelets from Unc13dJinx (Munc13-4 null) mice demonstrating a critical role for regulated membrane fusion in this process. Consistent with this observation, platelets efficiently converted fluorescent NBD-sphingosine to its phosphorylated derivative which accumulated in granules. Fractionation of platelet organelles revealed the presence of S1P in both the plasma membrane and in ?-granules. Resting platelets contained a second pool of constitutively releasable S1P that was more rapidly labeled by exogenously added sphingosine. Our studies indicate that platelets contain two pools of S1P that are released extracellularly: a readily-exchangeable, metabolically active pool of S1P, perhaps in the plasma membrane, and a granular pool that requires platelet activation and regulated exocytosis for release.
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