Syntheses of Sphingosine-1-phosphate Stereoisomers and Analogues and Their Interaction with EDG Receptors.

ChemInform ◽  
2003 ◽  
Vol 34 (18) ◽  
Author(s):  
Hyun-Suk Lim ◽  
Yong-Seok Oh ◽  
Pann-Ghill Suh ◽  
Sung-Kee Chung
Keyword(s):  
Edg Receptors ◽  
Sphingosine 1 Phosphate

Co-ordinate regulation of growth factor receptors and lipid phosphate phosphatase-1 controls cell activation by exogenous lysophosphatidate

2001 ◽  
Vol 29 (6) ◽  
pp. 825-830 ◽  
Author(s):  
C. Pilquil ◽  
Z.-C. Ling ◽  
I. Singh ◽  
K. Buri ◽  
Q.-X. Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Cell Activation ◽  
Growth Factor Receptors ◽  
Exogenous Lipid ◽  
Edg Receptors ◽  
Sphingosine 1 Phosphate ◽  
Lipid Phosphate ◽  
Lipid Phosphate Phosphatases ◽  
Differentiation Gene

The serum-derived lipid growth factors, lysophosphatidate (LPA) and sphingosine 1-phosphate (S1P), activate cells selectively through different members of a family of endothelial differentiation gene (EDG) receptors. Activation of EDG receptors by LPA and S1P provides a variety of signalling cascades depending upon the G-protein coupling of the different EDG receptors. This leads to chemotactic and mitogenic responses, which are important in wound healing. For example, LPA stimulates fibroblast division and S1P stimulates the chemotaxis and division of endothelial cells leading to angiogenesis. Counteracting these effects of LPA and S1P, are the actions of lipid phosphate phosphatases (LPP, or phosphatidate phosphohydrolases, Type 2). The isoform LPP-1 is expressed in the plasma membrane with its active site outside the cell. This enzyme is responsible for ‘ecto-phosphatase’ activity leading to the degradation of exogenous lipid phosphate mediators, particularly LPA. Expression of LPP-1 decreases cell activation by exogenous LPA. The mechanism for this is controversial and several mechanisms have been proposed. Evidence will be presented that the LPPs cross-talk with EDG and other growth factor receptors, thus, regulating the responses of the cells to lipid phosphate mediators of signal transduction.

scholarly journals Sphingosine 1-phosphate induces Ca2+ transients and cytoskeletal rearrangement in C2C12 myoblastic cells

2002 ◽  
Vol 282 (6) ◽  
pp. C1361-C1373 ◽  
Author(s):  
Lucia Formigli ◽  
Fabio Francini ◽  
Elisabetta Meacci ◽  
Massimo Vassalli ◽  
Daniele Nosi ◽  
...  
Keyword(s):  
Specific Inhibitor ◽  
Cell Contraction ◽  
Cytoskeletal Rearrangement ◽  
Edg Receptors ◽  
Inositol 1,4,5 Trisphosphate ◽  
Confocal Fluorescence ◽  
Sphingosine 1 Phosphate ◽  
Intracellular Ca ◽  
Confocal Fluorescence Imaging ◽  
Differentiation Gene

In many cell systems, sphingosine 1-phosphate (SPP) increases cytosolic Ca2+concentration ([Ca2+]i) by acting as intracellular mediator and extracellular ligand. We recently demonstrated (Meacci E, Cencetti F, Formigli L, Squecco R, Donati C, Tiribilli B, Quercioli F, Zecchi-Orlandini S, Francini F, and Bruni P. Biochem J 362: 349–357, 2002) involvement of endothelial differentiation gene (Edg) receptors (Rs) specific for SPP in agonist-mediated Ca2+ response of a mouse skeletal myoblastic (C2C12) cell line. Here, we investigated the Ca2+ sources of SPP-mediated Ca2+ transients in C2C12 cells and the possible correlation of ion response to cytoskeletal rearrangement. Confocal fluorescence imaging of C2C12 cells preloaded with Ca2+ dye fluo 3 revealed that SPP elicited a transient Ca2+ increase propagating as a wave throughout the cell. This response required extracellular and intracellular Ca2+ pool mobilization. Indeed, it was significantly reduced by removal of external Ca2+, pretreatment with nifedipine (blocker of L-type plasma membrane Ca2+channels), and inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]-mediated Ca2+pathway inhibitors. Involvement of EdgRs was tested with suramin (specific inhibitor of Edg-3). Fluorescence associated with Ins(1,4,5)P3Rs and L-type Ca2+channels was evident in C2C12 cells. SPP also induced C2C12 cell contraction. This event, however, was unrelated to [Ca2+]i increase, because the two phenomena were temporally shifted. We propose that SPP may promote C2C12 cell contraction through Ca2+-independent mechanisms.

Syntheses of sphingosine-1-phosphate stereoisomers and analogues and Their interaction with EDG receptors

2003 ◽  
Vol 13 (2) ◽  
pp. 237-240 ◽  
Author(s):  
Hyun-Suk Lim ◽  
Yong-Seok Oh ◽  
Pann-Ghill Suh ◽  
Sung-Kee Chung
Keyword(s):  
Edg Receptors ◽  
Sphingosine 1 Phosphate

scholarly journals Sphingosine 1-Phosphate and Activation of Endothelial Nitric-oxide Synthase

2001 ◽  
Vol 276 (15) ◽  
pp. 12420-12426 ◽  
Author(s):  
Junsuke Igarashi ◽  
Sylvie G. Bernier ◽  
Thomas Michel
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Enzyme Activity ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial ◽  
Enos Phosphorylation ◽  
Edg Receptors ◽  
Sphingosine 1 Phosphate ◽  
Oxide Synthase ◽  
G Protein Coupled

Sphingosine 1-phosphate (S1P) is a platelet-derived sphingolipid that elicits numerous biological responses in endothelial cells mediated by a family of G protein-coupled EDG receptors. Stimulation of EDG receptors by S1P has been shown to activate the endothelial isoform of nitric-oxide synthase (eNOS) in heterologous expression systems (Igarashi, J., and Michel, T. (2000)J. Biol. Chem.275, 32363–32370). However, the signaling pathways that modulate eNOS regulation by S1P/EDG in vascular endothelial cells remain less well understood. We now report that S1P treatment of bovine aortic endothelial cells (BAEC) acutely increases eNOS enzyme activity; the EC50for S1P activation of eNOS is ∼10 nm. The magnitude of eNOS activation by S1P in BAEC is equivalent to that elicited by the agonist bradykinin. S1P treatment activates Akt, a protein kinase implicated in phosphorylation of eNOS. S1P treatment of BAEC leads to eNOS phosphorylation at Ser1179, a residue phosphorylated by Akt; an eNOS mutant in which this Akt phosphorylation site is inactivated shows attenuated S1P-induced eNOS activation. S1P-induced activation both of Akt and of eNOS is inhibited by pertussis toxin, by the phosphoinositide 3-kinase inhibitor wortmannin, and by the intracellular calcium chelator BAPTA (1,2-bis(aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid). By contrast to S1P, activation of G protein-coupled bradykinin B2 receptors neither activates kinase Akt nor promotes Ser1179eNOS phosphorylation despite robustly activating eNOS enzyme activity. Understanding the differential regulation of protein kinase pathways by S1P and bradykinin may lead to the identification of new points for eNOS regulation in vascular endothelial cells.

Sphingosine 1-phosphate evokes calcium signals in C2C12 myoblasts via Edg3 and Edg5 receptors

2002 ◽  
Vol 362 (2) ◽  
pp. 349-357 ◽  
Author(s):  
Elisabetta MEACCI ◽  
Francesca CENCETTI ◽  
Lucia FORMIGLI ◽  
Roberta SQUECCO ◽  
Chiara DONATI ◽  
...  
Keyword(s):  
Laser Scanning ◽  
Biological Effects ◽  
Cell Types ◽  
Confocal Laser Scanning Microscope ◽  
C2c12 Cells ◽  
Confocal Laser ◽  
C2c12 Myoblasts ◽  
Edg Receptors ◽  
Sphingosine 1 Phosphate ◽  
Differentiation Gene

Sphingosine 1-phosphate (SPP) is a bioactive lipid that exerts multiple biological effects in a large variety of cell types, acting as either an intracellular messenger or an extracellular ligand coupled to Edg-family receptors (where Edg stands for endothelial differentiation gene). Here we report that in C2C12 myoblasts SPP elicited significant Ca2+ mobilization. Analysis of the process using a confocal laser-scanning microscope showed that the Ca2+ response occurred in a high percentage of cells, despite variations in amplitude and kinetics. Quantitative analysis of SPP-induced Ca2+ transients performed with a spectrophotofluorimeter showed that the rise in Ca2+ was strictly dependent on availability of extracellular Ca2+. Cell treatment with pertussis toxin partially prevented the Ca2+ response induced by SPP, indicating that Gi-coupled-receptors were involved. Indeed, SPP action was shown to be mediated by agonist-specific Edg receptors. In particular, suramin, an antagonist of the SPP-specific receptor Edg3, as well as down-regulation of Edg3 by cell transfection with antisense oligodeoxyribonucleotides (ODN), significantly reduced agonist-mediated Ca2+ mobilization. Moreover, an antisense ODN designed to inhibit Edg5 expression also decreased the SPP-induced rise in Ca2+, although to a lesser extent than that observed by inhibiting Edg3. On the contrary, the SPP response was unaffected in myoblasts loaded with antisense ODN specific for Edg1. Remarkably, the concomitant inhibition of Edg3 and Edg5 receptors abolished the SPP-induced Ca2+ increase, supporting the notion that Ca2+ mobilization in C2C12 cells induced by SPP is a receptor-mediated process that involves Edg3 and Edg5, but not Edg1.

scholarly journals Sphingosine 1-Phosphate Activates Nuclear Factor-κB through Edg Receptors

2001 ◽  
Vol 276 (52) ◽  
pp. 48733-48739 ◽  
Author(s):  
Sandra Siehler ◽  
Yuren Wang ◽  
Xiaomin Fan ◽  
Rolf T. Windh ◽  
David R. Manning
Keyword(s):  
Nuclear Factor Κb ◽  
Nuclear Factor ◽  
Edg Receptors ◽  
Sphingosine 1 Phosphate
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