Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan.
Int J Mol Med. 2011 May;27(5):695-700. doi: 10.3892/ijmm.2011.637. Epub 2011 Mar 3.
Elevation of cAMP in platelets is recognized to play a suppressive role in platelet functions. We have previously shown that adenosine diphosphate (ADP)-induced phosphorylation of heat shock protein 27 (HSP27) via p38 mitogen-activated protein (MAP) kinase is correlated with platelet-derived growth factor (PDGF)-AB secretion and soluble CD40 ligand (sCD40L) release. In the present study, we investigated the relationship between cAMP and HSP27 phosphorylation in platelet function. 8-Bromoadenosine-3',5'-cyclic monophosphate (8-bromo-cAMP), a plasma membrane-permeable cAMP analogue, or cilostazol, an inhibitor of cAMP phosphodiesterase, markedly attenuated the ADP-induced phosphorylation levels of p38 MAP kinase. In addition, the ADP-induced HSP27 phosphorylation was suppressed by 8-bromo-cAMP or cilostazol. 8-Bromo-cAMP, forskolin and cilostazol remarkably reduced the ADP-stimulated PDGF-AB secretion and sCD40L release. These results strongly suggest that cAMP regulates ADP-stimulated platelet activation due to inhibition of HSP27 phosphorylation via p38 MAP kinase.
血小板中环磷酸腺苷 (cAMP) 的升高被认为对血小板功能具有抑制作用。我们之前已经表明，通过 p38 丝裂原活化蛋白 (MAP) 激酶，二磷酸腺苷 (ADP) 诱导的热休克蛋白 27 (HSP27) 磷酸化与血小板衍生生长因子 (PDGF)-AB 分泌和可溶性 CD40 配体 (sCD40L) 释放有关。在本研究中，我们研究了 cAMP 与血小板功能中 HSP27 磷酸化之间的关系。8-溴代腺苷-3',5'-环单磷酸 (8-bromo-cAMP)，一种可透过质膜的 cAMP 类似物，或西洛他唑，一种 cAMP 磷酸二酯酶抑制剂，显著减弱了 ADP 诱导的 p38 MAP 激酶磷酸化水平。此外，8-bromo-cAMP 或 cilostazol 抑制 ADP 诱导的 HSP27 磷酸化。8-bromo-cAMP、forskolin 和 cilostazol 显著降低了 ADP 刺激的 PDGF-AB 分泌和 sCD40L 释放。这些结果强烈表明，cAMP 通过 p38 MAP 激酶抑制 HSP27 磷酸化来调节 ADP 刺激的血小板活化。
