HSP27 phosphorylation is correlated with ADP-induced platelet granule secretion.
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.
Kato
Hisaaki
H
Department of Pharmacology, Gifu University Graduate School of Medicine, Yanagido1-1, Gifu 501-1194, Japan.
Takai
Shinji
S
Matsushima-Nishiwaki
Rie
R
Adachi
Seiji
S
Minamitani
Chiho
C
Otsuka
Takanobu
T
Tokuda
Haruhiko
H
Akamatsu
Shigeru
S
Doi
Tomoaki
T
Ogura
Shinji
S
Kozawa
Osamu
O
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology
D005419:Flavonoids; D006360:Heat-Shock Proteins; D007093:Imidazoles; D011725:Pyridines; D000244:Adenosine Diphosphate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one