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

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

[1]  S. Hakomori,et al.  Quantification of free sphingosine in cultured cells by acylation with radioactive acetic anhydride. , 1994, Analytical biochemistry.

[2]  D. Gill,et al.  Sphingosine 1-phosphate generated in the endoplasmic reticulum membrane activates release of stored calcium. , 1994, The Journal of biological chemistry.

[3]  Y. Yatomi,et al.  Synthesis of phosphatidylinositol 3,4-bisphosphate is regulated by protein-tyrosine phosphorylation but the p85 alpha subunit of phosphatidylinositol 3-kinase may not be a target for tyrosine kinases in thrombin-stimulated human platelets. , 1994, Biochimica et biophysica acta.

[4]  G. Mannaerts,et al.  Sphinganine 1-phosphate metabolism in cultured skin fibroblasts: evidence for the existence of a sphingosine phosphatase. , 1994, The Biochemical journal.

[5]  L. Perkins,et al.  Identification and characterization of a lysophosphatidic acid receptor. , 1994, Molecular pharmacology.

[6]  S. Hourani,et al.  Receptors for ADP on human blood platelets. , 1994, Trends in pharmacological sciences.

[7]  S. Hakomori,et al.  Sphingosine‐1‐phosphate inhibits extracellular matrix protein‐induced haptotactic motility but not adhesion of B16 mouse melanoma cells , 1994, FEBS letters.

[8]  S. Laulederkind,et al.  Sphingosine-mediated phosphatidylinositol metabolism and calcium mobilization. , 1994, The Journal of biological chemistry.

[9]  S. Spiegel,et al.  Sphingosine-1-phosphate, a putative second messenger, mobilizes calcium from internal stores via an inositol trisphosphate-independent pathway. , 1994, The Journal of biological chemistry.

[10]  J. Sixma,et al.  Increased platelet deposition on atherosclerotic coronary arteries. , 1994, The Journal of clinical investigation.

[11]  S. Hakomori,et al.  Regulatory effect of phorbol esters on sphingosine kinase in BALB/C 3T3 fibroblasts (variant A31): demonstration of cell type-specific response--a preliminary note. , 1994, Biochemical and biophysical research communications.

[12]  Y. Hannun,et al.  Sphingolipid breakdown products: anti-proliferative and tumor-suppressor lipids. , 1993, Biochimica et biophysica acta.

[13]  S. Spiegel,et al.  Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens , 1993, Nature.

[14]  K. Lynch,et al.  Responses to sphingosine-1-phosphate in X. laevis oocytes: similarities with lysophosphatidic acid signaling. , 1993, The American journal of physiology.

[15]  I. Fahrenfort,et al.  The bioactive phospholipid lysophosphatidic acid is released from activated platelets. , 1993, The Biochemical journal.

[16]  R. Bell,et al.  Sphingosine kinase: properties and cellular functions. , 1993, Advances in lipid research.

[17]  S. Hakomori,et al.  Gangliosides and glycosphingolipids as modulators of cell growth, adhesion, and transmembrane signaling. , 1993, Advances in lipid research.

[18]  G. Mannaerts,et al.  Sphingosine-phosphate lyase. , 1993, Advances in lipid research.

[19]  S. Spiegel,et al.  Sphingosine-1-phosphate, a metabolite of sphingosine, increases phosphatidic acid levels by phospholipase D activation. , 1992, The Journal of biological chemistry.

[20]  S. Hakomori,et al.  Effect of sphingosine and its N-methyl derivatives on oxidative burst, phagokinetic activity, and trans-endothelial migration of human neutrophils. , 1992, Biochemical pharmacology.

[21]  S. Hakomori,et al.  Sphingosine 1-phosphate, a specific endogenous signaling molecule controlling cell motility and tumor cell invasiveness. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[22]  O. Hazeki,et al.  Suppression by wortmannin of platelet responses to stimuli due to inhibition of pleckstrin phosphorylation. , 1992, The Biochemical journal.

[23]  K. Jalink,et al.  Identification of a putative membrane receptor for the bioactive phospholipid, lysophosphatidic acid. , 1992, The EMBO journal.

[24]  R. Bell,et al.  Inhibition of sphingosine kinase in vitro and in platelets. Implications for signal transduction pathways. , 1992, The Journal of biological chemistry.

[25]  L. Parise,et al.  Platelet membrane glycoprotein IIb-IIIa complex: purification, characterization, and reconstitution into phospholipid vesicles. , 1992, Methods in enzymology.

[26]  G. Mannaerts,et al.  Subcellular localization and membrane topology of sphingosine-1-phosphate lyase in rat liver. , 1991, The Journal of biological chemistry.

[27]  S. Spiegel,et al.  Sphingosine-1-phosphate, a novel lipid, involved in cellular proliferation , 1991, The Journal of cell biology.

[28]  R. Kolesnick,et al.  Sphingomyelin synthesis is involved in adherence during macrophage differentiation of HL-60 cells. , 1991, The Journal of biological chemistry.

[29]  W. Siess.  Multiple Signal-Transduction Pathways Synergize in Platelet Activation , 1991 .

[30]  Y. Hannun,et al.  Use of D-erythro-sphingosine as a pharmacological inhibitor of protein kinase C in human platelets. , 1990, The Biochemical journal.

[31]  S. Hakomori.  Bifunctional role of glycosphingolipids. Modulators for transmembrane signaling and mediators for cellular interactions. , 1990, The Journal of biological chemistry.

[32]  K. Handa,et al.  A ceramide analogue inhibits T cell proliferative response through inhibition of glycosphingolipid synthesis and enhancement of N,N-dimethylsphingosine synthesis. , 1990, Biochemistry.

[33]  Y. Igarashi,et al.  A specific enhancing effect of N,N-dimethylsphingosine on epidermal growth factor receptor autophosphorylation. Demonstration of its endogenous occurrence (and the virtual absence of unsubstituted sphingosine) in human epidermoid carcinoma A431 cells. , 1990, The Journal of biological chemistry.

[34]  S. Hakomori,et al.  Enzymatic synthesis of N,N-dimethyl-sphingosine: demonstration of the sphingosine: N-methyltransferase in mouse brain. , 1989, Biochemical and biophysical research communications.

[35]  Kees Jalink,et al.  Lysophosphatidate-induced cell proliferation: Identification and dissection of signaling pathways mediated by G proteins , 1989, Cell.

[36]  S. Hakomori,et al.  Effect of chemically well-defined sphingosine and its N-methyl derivatives on protein kinase C and src kinase activities. , 1989, Biochemistry.

[37]  H. Arita,et al.  Possible involvement of cytoskeleton in collagen-stimulated activation of phospholipases in human platelets. , 1989, The Journal of biological chemistry.

[38]  R. Bell,et al.  A facile enzymatic synthesis of sphingosine-1-phosphate and dihydrosphingosine-1-phosphate. , 1989, Journal of lipid research.

[39]  M. B. Zucker,et al.  Platelet aggregation measured by the photometric method. , 1989, Methods in enzymology.

[40]  W. Siess.  Molecular mechanisms of platelet activation. , 1989, Physiological reviews.

[41]  J. Cazenave,et al.  Epinephrine potentiates human platelet activation but is not an aggregating agent. , 1988, The American journal of physiology.

[42]  S. Watson,et al.  The action of the protein kinase C inhibitor, staurosporine, on human platelets. Evidence against a regulatory role for protein kinase C in the formation of inositol trisphosphate by thrombin. , 1988, The Biochemical journal.

[43]  E. Lapetina,et al.  Decanoyl lysophosphatidic acid induces platelet aggregation through an extracellular action. Evidence against a second messenger role for lysophosphatidic acid. , 1985, The Biochemical journal.

[44]  Y. Nishizuka.  The role of protein kinase C in cell surface signal transduction and tumour promotion , 1984, Nature.

[45]  C. Dangelmaier,et al.  Differential energy requirements for platelet responses. A simultaneous study of aggregation, three secretory processes, arachidonate liberation, phosphatidylinositol breakdown and phosphatidate production. , 1982, The Biochemical journal.

[46]  J. Gerrard,et al.  Are lysophosphatidic acids or phosphatidic acids involved in stimulus activation coupling in platelets? , 1982, Blood.

[47]  Shin Lin,et al.  Cytochalasin D inhibits actin polymerization and induces depolymerization of actin filaments formed during platelet shape change , 1981, Nature.

[48]  N. Radin,et al.  Short chain ceramides as substrates for glucocerebroside synthetase. Differences between liver and brain enzymes. , 1979, Biochimica et biophysica acta.

[49]  G. Roth,et al.  Acetylation of the NH2-terminal serine of prostaglandin synthetase by aspirin. , 1978, The Journal of biological chemistry.

[50]  H. Patscheke,et al.  Platelet activation detected by turbidometric shape-change analysis: differential influence of cytochalasin B and prostaglandin E1. , 1978, Thrombosis research.

[51]  W. Stoffel,et al.  Sphingosine kinase in blood platelets. , 1973, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[52]  W. Stoffel,et al.  Properties and specificities of sphingosine kinase from blood platelets. , 1973, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[53]  W. Stoffel,et al.  Metabolism of sphingosine bases. 13. Enzymatic synthesis of 1-phosphate esters of 4t-sphingenine (sphingosine), sphinganine (dihydrosphingosine), 4-hydroxysphinganine (phytosphingosine) and 3-dehydrosphinganine by erythrocytes. , 1970, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[54]  W. J. Dyer,et al.  A rapid method of total lipid extraction and purification. , 1959, Canadian journal of biochemistry and physiology.

[55]  P. S. Chen,et al.  Microdetermination of Phosphorus , 1956 .