Sphingosine-1-phosphate: a platelet-activating sphingolipid released from agonist-stimulated human platelets.
Sphingosine-1-phosphate: a platelet-activating sphingolipid released from agonist-stimulated human platelets.
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DOI：
10.1182/blood.v86.1.193.bloodjournal861193
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发表时间：
1995-07
期刊：
影响因子：
20.3
通讯作者：
Yutaka Yatomi;Fuqiang Ruan;S. Hakomori;Yasuyuki Igarashi
中科院分区：
文献类型：
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作者：
Yutaka Yatomi;Fuqiang Ruan;S. Hakomori;Yasuyuki Igarashi
鞘氨醇-1-磷酸(Sph-1-P)是鞘氨醇被鞘氨醇激酶分解的初始产物，被Sph-1-P裂解酶裂解为脂肪醛和乙醇胺磷酸。这种磷酸化的狮身人面像碱基不仅是一种中间分解代谢物，而且是一种具有重要功能的生物活性脂质，包括刺激瑞士3T3成纤维细胞的细胞增殖和抑制肿瘤细胞的运动。在本研究中，我们研究了sph-1-P在人血小板中的功能作用。SPH-1-P虽不能诱导分泌，但可诱导血小板变形和聚集反应。鞘氨醇、神经酰胺、鞘磷脂和N，N-二甲基鞘氨醇不能模拟SPH-1-P对血小板的积极作用。亚阈值浓度的Sph-1-P与弱的血小板激动剂如二磷酸腺苷(ADP)和肾上腺素协同诱导聚集，这可能是有效放大血小板激活的重要因素。SPH-1-P可诱导细胞内钙离子的动员，钙离子释放的剂量效应与诱导细胞形态改变所需的浓度密切相关。在完整的血小板上加入[~3H]鞘氨醇后，标记迅速转化为SPH-1-P，随后转化为神经酰胺和鞘磷脂。有趣的是，在生理激动剂刺激下，形成的sph-1-P被特异性地释放到介质中。通过将其转化为放射性标记的N-乙酰-SPH-1-P，测得血小板中SPH-1-P的量为1.4nmol/10(9)个细胞，约为存在的Sph质量的4倍。以Sph-1-P/磷脂的摩尔百分比比较，血小板的值是中性粒细胞的10倍以上。我们的结果表明，sph-1-P由鞘氨醇迅速转化，大量储存在血小板中，并在细胞激活时释放，可能在血栓形成、止血和自然伤口愈合过程中发挥生理学作用。
Sphingosine-1-phosphate (Sph-1-P) is the initial product of catabolism of sphingosine by sphingosine kinase and is cleaved by Sph-1-P lyase to a fatty aldehyde and ethanolamine phosphate. This phosphorylated sphingoid base is not only an intermediary catabolite, but also a bioactive lipid with important functions, including stimulation of cell proliferation in Swiss 3T3 fibroblasts and inhibition of tumor cell motility. In the present study, we examined functional roles of Sph-1-P in human platelets. Sph-1-P induced platelet shape change and aggregation reactions, although it failed to elicit secretion. Sphingosine, ceramide, sphingomyelin, and N,N-dimethylsphingosine did not mimic the positive effects of Sph-1-P on platelets. Subthreshold concentrations of Sph-1-P and weak platelet agonists such as adenosine diphosphate (ADP) and epinephrine synergistically elicited aggregation, which may be important for efficient amplification of platelet activation. Sph-1-P induced intracellular Ca2+ mobilization and the dose-response for Ca2+ release correlated closely with the concentration required for induction of shape change. On addition of [3H]sphingosine to intact platelets, the label was rapidly converted to Sph-1-P, and subsequently to ceramide and sphingomyelin. Interestingly, the Sph-1-P formed was specifically released into medium on stimulation of platelets with physiologic agonists. The amount of Sph-1-P in platelets, as measured by its conversion into radiolabeled N-acetyl-Sph-1-P, was 1.4 nmol/10(9) cells and was about four times higher than the mass of Sph present. When compared by mole percent Sph-1-P/phospholipid, the value for platelets is over 10 times higher than that for neutrophils. Our results suggest that Sph-1-P, rapidly converted from sphingosine, abundantly stored in platelets, and released on the cell activation, may play a physiologic role in thrombosis, hemostasis, and the natural wound-healing processes.