Sphingosine-1-phosphate: a platelet-activating sphingolipid released from agonist-stimulated human platelets

摘要: Sphingosine-1-phosphate (Sph-1-P) is the initial product of catabolism sphingosine by kinase and cleaved Sph-1-P lyase to a fatty aldehyde ethanolamine phosphate. This phosphorylated sphingoid base not only an intermediary catabolite, but also bioactive lipid with important functions, including stimulation cell proliferation in Swiss 3T3 fibroblasts inhibition tumor motility. In present study, we examined functional roles human platelets. induced platelet shape change aggregation reactions, although it failed elicit secretion. Sphingosine, ceramide, sphingomyelin, N,N-dimethylsphingosine did mimic positive effects on Subthreshold concentrations weak agonists such as adenosine diphosphate (ADP) epinephrine synergistically elicited aggregation, which may be for efficient amplification activation. intracellular Ca2+ mobilization dose-response release correlated closely concentration required induction change. On addition [3H]sphingosine intact platelets, label was rapidly converted Sph-1-P, subsequently ceramide sphingomyelin. Interestingly, formed specifically released into medium platelets physiologic agonists. The amount measured its conversion radiolabeled N-acetyl-Sph- 1-P, 1.4 nmol/10(9) cells about four times higher than mass Sph present. When compared mole percent Sph-1- P/phospholipid, value over 10 that neutrophils. Our results suggest from sphingosine, abundantly stored activation, play role thrombosis, hemostasis, natural wound-healing processes.