Kato Hisaaki, Takai Shinji, Matsushima-Nishiwaki Rie, Adachi Seiji, Minamitani Chiho, Otsuka Takanobu, Tokuda Haruhiko, Akamatsu Shigeru, Doi Tomoaki, Ogura Shinji, Kozawa Osamu
Department of Pharmacology, Gifu University Graduate School of Medicine, Yanagido1-1, Gifu 501-1194, Japan.
Arch Biochem Biophys. 2008 Jul 1;475(1):80-6. doi: 10.1016/j.abb.2008.04.023. Epub 2008 Apr 29.
Adenosine diphosphate (ADP) plays a crucial role in hemostasis and thrombosis by activating platelets. ADP has been reported to induce heat-shock protein (HSP) 27 phosphorylation in human platelets. However, the exact role of HSP27 phosphorylation in human platelets has not yet been clarified. In the present study, we investigated the mechanisms and the roles of ADP-induced HSP27 phosphorylation in human platelets. We showed for the first time that both of decreased phosphorylation levels of HSP27 by PD98059, a MEK1/2 inhibitor and SB203580, a p38 MAPK inhibitor were correlated with the suppressed levels of platelet granule secretion but not with platelet aggregation. Furthermore, the inhibition of either the p44/p42 MAPK or p38 MAPK pathways had no effect on ADP-induced platelet aggregation. These results strongly suggest that the ADP-induced phosphorylation of HSP27 via p44/p42 MAPK and/or p38 MAPK is therefore sufficient for platelet granule secretion but not for platelet aggregation in humans.
二磷酸腺苷（ADP）通过激活血小板在止血和血栓形成中发挥关键作用。据报道，ADP可诱导人血小板中的热休克蛋白（HSP）27磷酸化。然而，HSP27磷酸化在人血小板中的确切作用尚未阐明。在本研究中，我们探讨了ADP诱导人血小板中HSP27磷酸化的机制及其作用。我们首次表明，MEK1/2抑制剂PD98059和p38丝裂原活化蛋白激酶（MAPK）抑制剂SB203580降低HSP27的磷酸化水平均与血小板颗粒分泌水平受抑制相关，但与血小板聚集无关。此外，抑制p44/p42 MAPK或p38 MAPK途径对ADP诱导的血小板聚集均无影响。这些结果有力地表明，因此，ADP通过p44/p42 MAPK和/或p38 MAPK诱导的HSP27磷酸化足以促进人血小板颗粒分泌，但不足以促进血小板聚集。
