title: AICAR reduces the collagen-stimulated secretion of PDGF-AB and release of soluble CD40 ligand from human platelets: Suppression of HSP27 phosphorylation via p44/p42 MAP kinase.
abstract: We have previously reported that collagen-induced phosphorylation of heat shock protein (HSP) 27 via p44/p42 mitogen-activated protein (MAP) kinase in human platelets is sufficient to induce the secretion of platelet-derived growth factor (PDGF)-AB and the release of soluble cluster of differentiation 40 ligand (sCD40L). Adenosine monophosphate-activated protein kinase (AMPK), which is known to regulate energy homeostasis, has a crucial role as an energy sensor in various eukaryotic cells. The present study investigated the effects of 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranosyl 5'-monophosphate (AICAR), which is an activator of AMPK, on the collagen-induced activation of human platelets. It was demonstrated that AICAR dose-dependently reduced collagen-stimulated platelet aggregation up to 1.0 µM. Analysis of the size of platelet aggregates demonstrated that AICAR decreased the ratio of large aggregates (50-70 µm), whereas the ratio of small aggregates (9-25 µm) was increased by AICAR administration. AICAR markedly attenuated the phosphorylation levels of p44/p42 MAP kinase and HSP27, which are induced by collagen. Furthermore, AICAR significantly decreased the secretion of PDGF-AB and the collagen-induced release of sCD40L. These results indicated that AICAR-activated AMPK may reduce the secretion of PDGF-AB and the collagen-induced release of sCD40L by inhibiting HSP27 phosphorylation via p44/p42 MAP kinase in human platelets.
authors.affiliation: Department of Neurosugery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Tsujimoto
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Clinical Laboratory, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Tokuda
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8603, Japan.
authors.forename: Gen
authors.initials: G
authors.lastname: Kuroyanagi
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8603, Japan.
authors.forename: Naohiro
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8603, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Kainuma
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Matsushima-Nishiwaki
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Onuma
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Iida
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan; Department of Anesthesiology and Critical Care Medicine, Matsunami General Hospital, Gifu 501-6062, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Kojima
authors.affiliation: Department of Neurosugery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Sawada
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Doi
authors.affiliation: Department of Neurosugery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Enomoto
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Kumiko
authors.initials: K
authors.lastname: Tanabe
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Matsunami General Hospital, Gifu 501-6062, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Akamatsu
authors.affiliation: Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Iida
authors.affiliation: Department of Emergency and Disaster Medicine, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Ogura
authors.affiliation: Department of Orthopedic Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8603, Japan.
authors.forename: Takanobu
authors.initials: T
authors.lastname: Otsuka
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
authors.affiliation: Department of Neurosugery, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Iwama
keywords: adenosine monophosphate-activated protein kinase; collagen; platelet-derived growth factor; platelets; soluble cluster of differentiation 40 ligand