title: Mechanism of collagen-induced release of 5-HT, PDGF-AB and sCD40L from human platelets: role of HSP27 phosphorylation via p44/p42 MAPK.
abstract: Collagen plays a crucial role in hemostasis and thrombosis by activating platelets and reportedly induces the phosphorylation of heat shock protein (HSP) 27 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 mechanism of collagen-induced HSP27 phosphorylation and the role in human platelets. The collagen-effect on the phospholylation of HSP27 was dose-dependent in the range between 0.03 and 1.0 microg/ml. The phosphorylation of p44/p42 mitogen-activated protein kinase (MAPK) was also stimulated by collagen. PD98059, a specific inhibitor of MAPK kinase (MEK1/2), reduced collagen-induced HSP27 phosphorylation as well as p44/p42 MAPK phosphorylation. PD98059 significantly suppressed collagen-induced releases of serotonin (5-HT), platelet-derived growth factor (PDGF)-AB and soluble CD40 ligand (sCD40L) while it had little effect on the platelet aggregation. These results strongly suggest that the collagen-induced phosphorylation of HSP27 via p44/p42 MAPK is sufficient for releases of 5-HT, PDGF-AB and sCD40L from human platelets.
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, and Department of Intensive Care Medicine, Matsunami General Hospital, Gifu, Japan.
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Kato
authors.forename: Seiji
authors.initials: S
authors.lastname: Adachi
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Doi
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Chiho
authors.initials: C
authors.lastname: Minamitani
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akamatsu
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Enomoto
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.forename: Toru
authors.initials: T
authors.lastname: Iwama
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
mesh_terms: D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D005419:Flavonoids; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006801:Humans; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000494:pharmacology; D018832:Molecular Chaperones; D010766:Phosphorylation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism* / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology
chemical_list: D005419:Flavonoids; D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010982:Platelet-Derived Growth Factor; C095477:platelet-derived growth factor AB; D023201:CD40 Ligand; D012701:Serotonin; D003094:Collagen; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one