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Thrombopoietin amplifies ADP-induced HSP27 phosphorylation in human platelets: Importance of pre-treatment

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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.
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Document Type: Research Article

Affiliations: 1: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan 2: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan 3: Department of Anesthesiology and Critical Care Medicine, Matsunami General Hospital, Gifu 501-6062, Japan 4: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan

Publication date: January 1, 2013

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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