title: HSP27 phosphorylation is correlated with ADP-induced platelet granule secretion.
abstract: 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.
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Yanagido1-1, Gifu 501-1194, Japan.
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Kato
authors.forename: Shinji
authors.initials: S
authors.lastname: Takai
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Seiji
authors.initials: S
authors.lastname: Adachi
authors.forename: Chiho
authors.initials: C
authors.lastname: Minamitani
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akamatsu
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Doi
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: 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
chemical_list: 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