title: Thrombopoietin amplifies ADP-induced HSP27 phosphorylation in human platelets: importance of pre-treatment.
abstract: It has been shown that thrombopoietin (TPO) amplifies agonist-induced platelet activation. However, the precise mechanism of action of TPO has not yet been fully elucidated. We have previously reported that the adenosine diphosphate (ADP)‑induced phosphorylation of heat shock protein 27 (HSP27) via the p38 mitogen-activated protein (MAP) kinase pathway correlates with the ADP-induced platelet-derived growth factor (PDGF)-AB secretion and the release of soluble CD40 ligand (sCD40L) from human platelets. In the present study, we investigated the effects of TPO on platelet activation induced by ADP. We examined the effects of TPO on ADP-induced platelet activation under different treatments: TPO was administered 15 min prior to stimulation with ADP (pre-treatment); TPO and ADP were simultaneously administered (simultaneous treatment); and TPO was administered 2 min following stimulation with ADP (post-treatment). TPO, which alone had no effect on platelet aggregation, synergistically enhanced the ADP (1 mM)-induced platelet aggregation only when it was administered prior to stimulation with ADP. Pre-treatment with TPO significantly increased the secretion of PDGF-AB and the release of sCD40L, and markedly enhanced the ADP-induced phosphorylation of p38 MAP kinase and HSP27 in the platelets. However, simultaneous treatment with TPO or TPO post-treatment failed to affect the ADP-induced platelet aggregation, the secretion of PDGF-AB, the release of sCD40L and the phosphorylation p38 MAP kinase or HSP27. These results strongly suggest that pre-treatment with TPO significantly amplifies ADP-induced HSP27 phosphorylation via the p38 MAP kinase pathway in human platelets.
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Nguyen The
authors.initials: NT
authors.lastname: Cuong
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Doi
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akamatsu
authors.forename: Gen
authors.initials: G
authors.lastname: Kuroyanagi
authors.forename: Akira
authors.initials: A
authors.lastname: Kondo
authors.forename: Jun
authors.initials: J
authors.lastname: Mizutani
authors.forename: Ikuo
authors.initials: I
authors.lastname: Wada
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D013926:Thrombopoietin / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D055551:HSP27 Heat-Shock Proteins; D010982:Platelet-Derived Growth Factor; C095477:platelet-derived growth factor AB; D023201:CD40 Ligand; D000244:Adenosine Diphosphate; D013926:Thrombopoietin; D048051:p38 Mitogen-Activated Protein Kinases