Sphingosine 1-phosphate as a major bioactive lysophospholipid that is released from platelets and interacts with endothelial cells

作     者：Yatomi, Y Ohmori, T Ge, RL Kazama, F Okamoto, H Sano, T Satoh, K Kume, S Tigyi, G Igarashi, Y Ozaki, Y 

作者机构：Yamanashi Med Univ Dept Lab Med Yamanashi 4093898 Japan Hokkaido Univ Grad Sch Pharmaceut Sci Dept Biomembrane & Biofunct Chem Sapporo Hokkaido Japan Univ Tennessee Ctr Hlth Sci Dept Physiol Memphis TN 38163 USA 

出 版 物：《BLOOD》 (血液)

年 卷 期：2000年第96卷第10期

页      面：3431-3438页

核心收录：

学科分类：1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

主　　题：生物转运 血小板/代谢 钙信号/药物作用 细胞运动/药物作用 色谱法 薄层 细胞骨架/药物作用 内皮 血管/细胞学 内皮 血管/代谢 胎血/细胞学 胎血/代谢 溶血磷脂素类/分离和提纯 溶血磷脂素类/代谢 磷酸盐类/诊断应用 磷酸盐类/代谢 磷放射性同位素/诊断应用 RNA 信使/代谢 受体 细胞表面/遗传学 受体 G-蛋白偶联 受体 溶血磷脂酸 受体 溶血磷脂 血清白蛋白/药理学 鞘氨醇/类似物和衍生物 鞘氨醇/代谢 人类 

摘      要：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 [P-32]Sph-1-P, but not [P-32]LPA, was observed In [P-32]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. (C) 2000 by The American Society of Hematology.