TY - JOUR
T1 - cAMP regulates ADP-induced HSP27 phosphorylation in human platelets
AU - Enomoto, Yukiko
AU - Adachi, Seiji
AU - Doi, Tomoaki
AU - Natsume, Hideo
AU - Kato, Kenji
AU - Matsushima-Nishiwaki, Rie
AU - Akamatsu, Shigeru
AU - Tokuda, Haruhiko
AU - Yoshimura, Shinichi
AU - Otsuka, Takanobu
AU - Ogura, Shinji
AU - Kozawa, Osamu
AU - Iwama, Toru
PY - 2011/5
Y1 - 2011/5
N2 - 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.
AB - 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.
KW - Adenosine diphosphate
KW - Cilostazol
KW - DP
KW - Heat shock protein 27
KW - Phosphorylation
KW - Platelet
KW - cAMP
UR - http://www.scopus.com/inward/record.url?scp=79952914929&partnerID=8YFLogxK
U2 - 10.3892/ijmm.2011.637
DO - 10.3892/ijmm.2011.637
M3 - 学術論文
C2 - 21373747
AN - SCOPUS:79952914929
SN - 1107-3756
VL - 27
SP - 695
EP - 700
JO - International Journal of Molecular Medicine
JF - International Journal of Molecular Medicine
IS - 5
ER -