Sphingosine 1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells.
The serum-borne lysophospholipid mediators sphingosine 1-phosphate (Sph-1-P) and lysophosphatidic acid (LPA) have been shown to be released from activated platelets and to act on endothelial cells. In this study, we employed the repeated lipid extraction (under alkaline and acidic conditions), capable of detecting Sph-1-P, LPA, and possibly structurally similar lysophospholipids, whereby a marked formation of [(32)P]Sph-1-P, but not [(32)P]LPA, was observed in [(32)P]orthophosphate-labeled platelets. Platelet Sph-1-P release, possibly mediated by protein kinase C, was greatly enhanced in the presence of albumin, which formed a complex with Sph-1-P. This finding suggests that platelet Sph-1-P may become accessible to depletion by albumin when its transbilayer movement (flipping) across the plasma membrane is enhanced by protein kinase C. Although human umbilical vein endothelial cells expressed receptors for both Sph-1-P and LPA, Sph-1-P acted much more potently than LPA on the cells in terms of intracellular Ca(++) mobilization, cytoskeletal reorganization, and migration. The results suggest that Sph-1-P, rather than LPA, is a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells, under the conditions in which critical platelet-endothelial interactions (including thrombosis, angiogenesis, and atherosclerosis) occur. Furthermore, albumin-bound Sph-1-P may account for at least some of the serum biological activities on endothelial cells, which have been ascribed to the effects of albumin-bound LPA, based on the similarities between LPA and serum effects.
Yatomi
Y
Y
Department of Laboratory Medicine, Yamanashi Medical University, Nakakoma, Japan. yatomiy@res.yamanashi-med.ac.jp
Ohmori
T
T
Rile
G
G
Kazama
F
F
Okamoto
H
H
Sano
T
T
Satoh
K
K
Kume
S
S
Tigyi
G
G
Igarashi
Y
Y
Ozaki
Y
Y
D001692:Biological Transport; D001792:Blood Platelets / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002855:Chromatography, Thin Layer; D003599:Cytoskeleton / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000302:isolation & purification / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010761:Phosphorus Radioisotopes; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049312:Receptors, Lysophospholipid; D012709:Serum Albumin / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000378:metabolism*
D008246:Lysophospholipids; D010710:Phosphates; D010761:Phosphorus Radioisotopes; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D049368:Receptors, Lysophosphatidic Acid; D049312:Receptors, Lysophospholipid; D012709:Serum Albumin; C060506:sphingosine 1-phosphate; D013110:Sphingosine