cAMP regulates ADP-induced HSP27 phosphorylation in human platelets
cAMP regulates ADP-induced HSP27 phosphorylation in human platelets
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DOI：
10.3892/ijmm.2011.637
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发表时间：
2011-05-01
影响因子：
5.4
通讯作者：
Iwama, Toru
中科院分区：
文献类型：
--
作者：
Enomoto, Yukiko;Adachi, Seiji;Iwama, Toru
血小板中cAMP的升高被认为对血小板功能具有抑制作用。我们先前已经证明，二磷酸腺苷(ADP)通过p38丝裂原活化蛋白(MAP)激酶诱导热休克蛋白27(HSP27)的磷酸化与血小板衍生生长因子(PDGF)-AB的分泌和可溶性CD40配体(SCD40L)的释放有关。在本研究中，我们探讨了cAMP和HSP27磷酸化与血小板功能的关系。质膜通透性cAMP类似物8-溴腺苷-3‘，5’-环磷腺苷(8-bromo-cAMP)或cAMP磷酸二酯酶抑制剂西洛他唑可显著减弱ADP诱导的p38 MAP激酶的磷酸化水平。此外，8-溴-cAMP或西洛他唑可抑制ADP诱导的H5P27的磷酸化。8-溴-cAMP、福司可林和西洛他唑显著抑制ADP刺激的PDGF-AB分泌和sCD40L释放。这些结果有力地表明，cAMP通过p38 MAP激酶抑制HSP27的磷酸化，从而调节ADP刺激的血小板激活。
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 H5P27 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.