cAMP regulates ADP-induced HSP27 phosphorylation in human platelets

Enomoto,Yukiko; Adachi,Seiji; Doi,Tomoaki; Natsume,Hideo; Kato,Kenji; Matsushima-Nishiwaki,Rie; Akamatsu,Shigeru; Tokuda,Haruhiko; Yoshimura,Shinichi; Otsuka,Takanobu; Ogura,Shinji; Kozawa,Osamu; Iwama,Toru

doi:10.3892/ijmm.2011.637

cAMP regulates ADP-induced HSP27 phosphorylation in human platelets

Authors:
- Yukiko Enomoto
- Seiji Adachi
- Tomoaki Doi
- Hideo Natsume
- Kenji Kato
- Rie Matsushima-Nishiwaki
- Shigeru Akamatsu
- Haruhiko Tokuda
- Shinichi Yoshimura
- Takanobu Otsuka
- Shinji Ogura
- Osamu Kozawa
- Toru Iwama
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Affiliations: Department of Neurosurgery, Gifu University Graduate School of Medicine, Gifu, Japan, Department of Pharmacology, Gifu University Graduate School of Medicine, Yanagido1-1, Gifu 501-1194, Japan
Published online on: March 3, 2011 https://doi.org/10.3892/ijmm.2011.637
Pages: 695-700

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Abstract

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.