Aoki Shinya, Osada Makoto, Kaneko Makoto, Ozaki Yukio, Yatomi Yutaka
Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Biochem Biophys Res Commun. 2007 Jul 13;358(4):1054-7. doi: 10.1016/j.bbrc.2007.05.028. Epub 2007 May 14.
Fluid shear stress modulates the functional responses of platelets and vascular cells, and plays an important role in the pathogenesis of vascular disorders, including atherosclerosis and restenosis. Since shear stress induces activation of platelets, which abundantly store sphingosine 1-phosphate (Sph-1-P), and upregulates the mRNA expression of S1P(1), the most important Sph-1-P receptor expressed on the endothelial cells, we examined the effects of shear stress on the Sph-1-P-related responses involving these cells. Shear stress was found to induce Sph-1-P release from the platelets in a shear intensity- and time-dependent manner. Inhibitors of protein kinase C suppressed this mechanical force-induced Sph-1-P release, suggesting involvement of this kinase. On the other hand, in vascular endothelial cells, shear stress increased S1P(1) protein expression, as revealed by flow-cytometric analysis, and the responsiveness to Sph-1-P, which was assessed by monitoring the intracellular Ca(2+) concentration. These results indicate that shear stress enhances the Sph-1-P responses in cell-cell interactions between platelets and endothelial cells.
流体剪切应力调节血小板和血管细胞的功能反应，并在包括动脉粥样硬化和再狭窄在内的血管疾病发病机制中起重要作用。由于剪切应力可诱导血小板活化，血小板大量储存鞘氨醇-1-磷酸（Sph-1-P），并上调内皮细胞上表达的最重要的Sph-1-P受体S1P(1)的mRNA表达，因此我们研究了剪切应力对涉及这些细胞的Sph-1-P相关反应的影响。发现剪切应力以剪切强度和时间依赖性方式诱导血小板释放Sph-1-P。蛋白激酶C抑制剂可抑制这种机械力诱导的Sph-1-P释放，提示该激酶参与其中。另一方面，在血管内皮细胞中，流式细胞术分析显示剪切应力增加了S1P(1)蛋白表达，并通过监测细胞内Ca(2+)浓度评估了对Sph-1-P的反应性。这些结果表明，剪切应力增强了血小板与内皮细胞之间细胞-细胞相互作用中的Sph-1-P反应。
