Hisano N, Yatomi Y, Fujino M A, Igarashi Y, Kume S, Ozaki Y
Department of Laboratory Medicine, Yamanashi Medical University.
J Biochem. 1998 Feb;123(2):263-8. doi: 10.1093/oxfordjournals.jbchem.a021931.
To elucidate the physiologic role of sphingolipid-derived products as signaling molecules, we analyzed the levels of endogenous sphingosine (Sph) derivatives in human platelets. When the platelets were stimulated with thrombin or 12-O-tetradecanoylphorbol 13-acetate, neither ceramide formation nor sphingomyelin hydrolysis was observed, which suggests that the sphingomyelin cycle may not be an essential part of the signaling pathway under these conditions. In contrast, Sph was found to increase in platelets upon stimulation. The level of Sph 1-phosphate, which is formed from Sph by the action of Sph kinase, was not affected under our conditions. Although it has been established that Sph inhibits protein kinase C, which regulates the functional responses of the platelets, Sph levels which exert an inhibitory effect on protein kinase C cannot be attained under physiological conditions (without exogenous Sph). Considering the stimulation of the synthesis of Sph by the physiological agonist thrombin, we speculate that Sph is a signaling molecule of physiological importance in platelets, but protein kinase C may not be its target.
为阐明鞘脂衍生产物作为信号分子的生理作用，我们分析了人血小板中内源性鞘氨醇（Sph）衍生物的水平。当用凝血酶或12 - O - 十四烷酰佛波醇13 - 乙酸酯刺激血小板时，未观察到神经酰胺的形成或鞘磷脂的水解，这表明在这些条件下鞘磷脂循环可能不是信号通路的必要组成部分。相反，发现刺激后血小板中的Sph增加。在我们的条件下，由Sph激酶作用于Sph形成的1 - 磷酸鞘氨醇水平未受影响。尽管已经确定Sph抑制调节血小板功能反应的蛋白激酶C，但在生理条件下（无外源性Sph）无法达到对蛋白激酶C产生抑制作用的Sph水平。考虑到生理激动剂凝血酶对Sph合成的刺激作用，我们推测Sph是血小板中具有重要生理意义的信号分子，但蛋白激酶C可能不是其作用靶点。
