Showing papers on "Sphingosine-1-phosphate published in 1997"
TL;DR: The release of Sph-1-P from activated platelets may be involved in a variety of physiological and pathophysiological processes, including thrombosis, hemostasis, atherosclerosis and wound healing.
Abstract: Although sphingosine 1-phosphate (Sph-1-P) is reportedly involved in diverse cellular processes and the physiological roles of this bioactive sphingolipid have been strongly suggested, few studies have revealed the presence of Sph-1-P in human samples, including body fluids and cells, under physiological conditions. In this study, we identified Sph-1-P as a normal constituent of human plasma and serum. The Sph-1-P levels in plasma and serum were 191+/-79 and 484+/-82 pmol/ml (mean+/-SD, n=8), respectively. Furthermore, when Sph-1-P was measured in paired plasma and serum samples obtained from 6 healthy adults, the serum Sph-1-P/plasma Sph-1-P ratio was found to be 2.65+/-1.26 (mean+/-SD). It is most likely that the source of discharged Sph-1-P during blood clotting is platelets, because platelets abundantly store Sph-1-P compared with other blood cells, and release part of their stored Sph-1-P extracellularly upon stimulation. We also studied Sph-1-P-related metabolism in plasma. [3H]Sph was stable and not metabolized at all in plasma, but was rapidly incorporated into platelets and metabolized mainly to Sph-1-P in platelet-rich plasma. [3H]Sph-1-P was found to be unchanged in plasma, revealing that plasma does not contain the enzymes needed for Sph-1-P degradation. In summary, platelets can convert Sph into Sph-1-P, and are storage sites for the latter in the blood. In view of the diverse biological effects of Sph-1-P, the release of Sph-1-P from activated platelets may be involved in a variety of physiological and pathophysiological processes, including thrombosis, hemostasis, atherosclerosis and wound healing.
451 citations
TL;DR: The results suggest that activation of sphingosine kinase and subsequent formation of SPP may play an important role in the differentiation and survival effects induced by NGF.
Abstract: Sphingolipid metabolites, such as ceramide and sphingosine-1-phosphate (SPP), are emerging as a new class of second messengers involved in cellular proliferation, differentiation, and apoptosis. Nerve growth factor (NGF), a neurotrophic factor for pheochromocytoma PC12 cells, induced a biphasic increase in the activity of sphingosine kinase, the enzyme that catalyzes the formation of SPP. This activation was blocked by K252a, an inhibitor of tyrosine kinase A (trkA). A rapid 1.7-fold increase was followed by a marked prolonged increase reaching a maximum of fourfold to fivefold stimulation with a concomitant increase in SPP levels and a corresponding decrease in endogenous sphingosine levels. Levels of ceramide, the precursor of sphingosine, were only slightly decreased by NGF in serum-containing medium. However, NGF decreased the elevation of ceramide induced by serum withdrawal. Treatment of PC12 cells with SPP did not induce neurite outgrowth or neurofilament expression, yet it enhanced neurofilament expression elicited by suboptimal doses of NGF. Moreover, SPP also protected PC12 cells from apoptosis induced by serum withdrawal. To further substantiate a role for SPP in the cytoprotective actions of NGF, we found that N, N-dimethylsphingosine, a competitive inhibitor of sphingosine kinase, also induced apoptosis and interfered with the survival effect of NGF. These effects were counteracted by exogenous SPP. Moreover, other structurally related compounds, such as dihydrosphingosine 1-phosphate and lysophosphatidic acid, had no significant protective effects. Our results suggest that activation of sphingosine kinase and subsequent formation of SPP may play an important role in the differentiation and survival effects induced by NGF.
288 citations
TL;DR: Results suggest that Sph-1-P acts not intracellularly but intercellularly, following discharge from activated platelets, and shares a platelet surface receptor with LPA.
206 citations
TL;DR: The recent conceptual developments on sphingolipid signaling pathways is outlined and the perspective of future sphingosine research (sphingology or sphingophysiology) is briefly discussed.
Abstract: The signaling roles of ceramide and sphingosine produced through the degrading processes of membrane sphingolipids are currently receiving hot attention in the biochemical and biomedical research fields. For these 9 years at the Biomembrane Institute in Seattle, we have studied functional roles of various sphingolipids such as ceramide, sphingosine, methylsphingosines, and sphingosine 1-phosphate in a variety of biomedical systems. In this article, first, the recent conceptual developments on sphingolipid signaling pathways is outlined. Next, our recent findings on the functional roles of sphingolipids are described focusing on (i) functional roles of sphingosine 1-phosphate in cell motility regulation and platelet activation (ii) involvement of sphingosine in cell signaling (iii) effects of methylsphingosines in cancer cell apoptosis induction and in the regulation of inflammatory processes. Based upon these findings from our studies and others, the perspective of future sphingosine research (sphingology or sphingophysiology) is briefly discussed.
139 citations
TL;DR: Regulation of sphingosine kinase activity defines divergence in signal transduction pathways of PDGF and EGF receptors leading to mitogen-activated protein kinase activation.
118 citations
TL;DR: Observations on supposed sphingolipid second messenger actions deserve a new evaluation, and ligand profiles and concentration‐response relationships suggest the existence of putative sphingosine 1‐phosphate‐based receptor subtypes.
102 citations
TL;DR: Of the growth factors examined, NGF was the most potent activator of sphingosine kinase, inducing a 4‐fold increase in V max, and may have an important role in neural differentiation.
100 citations
TL;DR: It is found that among various sphingosine derivatives, Sph‐1‐P specifically inhibited the IL‐8‐ or fLMP‐induced chemotactic migration of neutrophils at concentrations below 1 μM, raising the possibility of future applications of Sph‐ 1‐P, or its analogs, as anti‐inflammatory agents regulating invasive migration of Neutrophils through endothelial layers at injured vascular sites.
84 citations
TL;DR: The results strongly suggest that Sph-1-P regulates melanoma cell motility through an extracellular action by specific binding to cell surface receptor protein(s), which is independent of PTX-sensitive G-protein.
Abstract: Our previous work showed that sphingosine 1-phosphate (Sph-1-P) inhibits the cell motility of mouse melanoma B16/F10, and other types of cells at 10-100 nM concentrations. In the present paper, we have identified and characterized specific cell surface binding sites for Sph-1-P in F10 cells. Sph-1-P immobilized on controlled pore glass beads inhibited the motility of F10 cells, suggesting that Sph-1-P acts on the cells from the outside. Binding assays with [3H]Sph-1-P revealed the presence of specific cell surface binding sites for Sph-1-P in F10 cells. Scatchard analysis demonstrated a single class of binding sites for Sph-1-P. The binding of [3H]Sph-1-P to F10 cells was inhibited by the addition of excess unlabeled Sph-1-P but not other natural sphingolipids. The specific binding was also sensitive to treatment with a protease. Using Sph-1-P-immobilized affinity chromatography, we, for the first time, identified 41-kDa and 79-kDa Sph-1-P binding proteins on the melanoma cell surface, although the 41-kDa protein was less specific to Sph-1-P. We demonstrated that pertussis toxin (PTX) treatment did not abolish the motility inhibition by Sph-1-P, suggesting that no PTX-sensitive G-protein is involved in the signaling. Furthermore, Sph-1-P was found to be specifically released from mouse BALB/3T3 clone A31 cells and F10 cells. Collectively, these results strongly suggest that Sph-1-P regulates melanoma cell motility through an extracellular action by specific binding to cell surface receptor protein(s), which is independent of PTX-sensitive G-protein.
83 citations
TL;DR: The results suggest that the exogenous S1P-induced shape change does not require uptake of the lipid into the cells but possibly requires interaction with a cell surface receptor in the neuronal cells.
73 citations
TL;DR: In serum-starved NIH 3T3 clone 7 fibroblasts, choline phosphate (ChoP) and insulin synergistically stimulate DNA synthesis and ChoP induces mitogenesis through an extracellular site by mechanisms involving the activation of pp70 S6 kinase and, to a lesser extent, PI 3′-kinase.
TL;DR: In this article, the authors investigated the mechanism of IL-6 synthesis induced by tumor necrosis factor-α (TNF) in osteoblast-like MC3T3-E1 cells.
TL;DR: It is suggested that the use of nanofiltration membranes for the recovery of phosphorous with a second type of technology is a viable process and should be considered as a possibility for further research.
TL;DR: It is concluded that S-1-P, through an LPA receptor-independent mechanism, stimulates two signaling pathways, i.e., activation of the PLC-Ca2+ system and inhibition of adenylyl cyclase, through distinct S- 1-P receptor-transducer systems, resulting in the modulation of glycogenolysis in rat hepatocytes.
Abstract: Sphingosine 1-phosphate (S-1-P) and lysophosphatidic acid (LPA) stimulated glycogen phosphorylase, a rate-limiting enzyme responsible for glycogenolysis, in association with Ca2+ mobilization and p...
TL;DR: Data indicate that SPP activates a tyrosine kinase that phosphorylates Crk and that Crk is a positive effector of SPP-induced mitogenesis, which appears to be Ras-dependent, whereas SPP stimulation of MAP kinase activity is Ras-independent.
TL;DR: The results indicate that the synergistic mitogenic effects of PCho and S1P are not restricted to NIH 3T3 fibroblasts, are predominantly mediated by the MAP kinase‐dependent signal transduction pathway, and are enhanced by ethanolamine via a MAP kin enzyme‐independent mechanism.
TL;DR: The results suggest that sphingosine activates phospholipase C through a mechanism functionally coupled through a G protein and under control of PKC.
01 Jan 1997
TL;DR: Current knowledge regarding the second messenger role of SPP in regulating the fate of the cell is focused on current knowledge about sphingosine-1-phosphate.
Abstract: Homeostasis of multicellular organisms as well as their normal development depends on the balance between cellular proliferation, differentiation, and cell death or apoptosis. Ceramide, sphingosine, and sphingosine-1-phosphate (SPP), metabolites of sphingolipids, and ubiquitous components of eukaryotic cell membranes, have recently emerged as members of a new class of signaling molecules regulating these diverse cellular processes.1–4 Sphingolipid metabolism involves removal of their polar headgroups; for example, phosphorylcholine from sphingomyelin by acidic or neutral sphingomyelinases to produce ceramide,5 which can then be cleaved by ceramidases to release fatty acid and the free long-chain base (sphingosine or sphinganine).6 Sphingosine can be phosphorylated to SPP by sphingosine kinase,7 reacylated to ceramide, or methylated.8 SPP in turn can undergo dephosphorylation to sphingosine,9 or cleavage to ethanolamine phosphate and trans-2hexadecenal by a pyridoxal phosphate-dependent lyase.10,11 Although all of these sphingolipid metabolites may play important roles in cell regulation, this review is focused on current knowledge regarding the second messenger role of SPP in regulating the fate of the cell.