| Research Abstract |
Sphingosine 1-phosphate (S1P) exerts a variety of cellular responses including proliferation, differentiation, adhesion, motility and apoptosis through G-protein-coupled S1P receptors (Edg-I, -3, -5, -6, -8). Here, we established a novel quantitative method for S1P and investigated its function and action mechanisms. (1) We established a novel quantitative method for S1P based on the ligand competition on S1P receptor Edg-1. We found that the tight binding of S1P to the lipoproteins especially HDL may interferes with S1P binding to its receptors and thereby might protect the cells from "over-activation" of S1P receptors. (2) It is well known that HDL is inversely correlated with the risk of cardiovascular disease, such as atherosclerosis. The pharmacological and molecular biological analyzes demonstrated that S1P is a major component of HDL in the lipoprotein-induced endothelial cell migration and survival. The HDL or lipid-induced actions may be mediated through the lipid receptors, S1P_1/Edg-1 and S1P_3 /Edg-3.(3) In rat type I astrocytes and C6 glioma cells, we found a differential roles of Edg-1 (stimulation of Erk/bFGF system) and Edg-5 (increase in intracellular calcium concentration and stimulation phospholipase C and D). We also found that HDL mimicked these actions and their actions are mediated by S1P/S1P receptors. Thus, S1P might partially mediate lipoprotein-induced cholesterol metabolism-independent neural cell functions in the central nervous system
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