Sphingosine 1-phosphate stimulates proliferation and migration of human endothelial cells possibly through the lipid receptors, Edg-1 and Edg-3

Citation
T. Kimura et al., Sphingosine 1-phosphate stimulates proliferation and migration of human endothelial cells possibly through the lipid receptors, Edg-1 and Edg-3, BIOCHEM J, 348, 2000, pp. 71-76
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL JOURNAL
ISSN journal
0264-6021 → ACNP
Volume
348
Year of publication
2000
Part
1
Pages
71 - 76
Database
ISI
SICI code
0264-6021(20000515)348:<71:S1SPAM>2.0.ZU;2-F
Abstract
Sphingosine 1-phosphate (S1P) stimulates thymidine incorporation (DNA synth esis), cell growth and cell migration in human aortic endothelial cells (HA ECs). The extent of the S1P-induced responses are comparable to those stimu lated by vascular endothelial growth factor, one of the most potent stimula tors of angiogenesis. These responses to SIP were mimicked by dihydrosphing osine l-phosphate, an SIP receptor agonist, and inhibited by pertussis toxi n (PTX), an inactivator of G(i)/G(o)-proteins. SLP also induced activation of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated pr otein kinase (p38 MAP kinase). The activation of these enzymes was inhibite d again by PTX and also by suramin, a non-selective receptor antagonist. SI P-induced DNA synthesis and ERK activation were inhibited by PD98059, an ER K kinase inhibitor, but not by SB203580, a p38 MAP kinase inhibitor. In con trast, cell migration and p38 MAP kinase activation, in response to S1P, we re inhibited by SB203580 but not by PD98059. In HAECs, high-affinity S1P bi nding activity and expression of Edg-1 and Edg-3 mRNA were detected. These results suggest that SIP might be a novel angiogenesis factor and that the lipid-induced proliferation and migration of endothelial cells are possibly mediated through cell-surface S1P receptors, Edg-1 and Edg-3, which are li nked to signalling pathways.