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

作者：Tsujimoto Masanori; Tokuda Haruhiko^*; Kuroyanagi Gen; Yamamoto Naohiro; Kainuma Shingo; Matsushima Nishiwaki Rie; Onuma Takashi; Iida Yuko; Kojima Akiko; Sawada Shigenobu; Doi Tomoaki; Enomoto Yukiko; Tanabe Kumiko; Akamatsu Shigeru; Iida Hiroki; Ogura Shinji; Otsuka Takanobu; Kozawa Osamu; Iwama Toru

来源：Experimental and Therapeutic Medicine, 2016, 12(2): 1107-1112.

DOI：10.3892/etm.2016.3435

• adenosine monophosphate-activated protein kinase
• collagen
• platelet-derived growth factor
• soluble cluster of differentiation 40 ligand
• platelets

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-carbox amide-1-beta-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 mu M. Analysis of the size of platelet aggregates demonstrated that AICAR decreased the ratio of large aggregates (50-70 mu m), whereas the ratio of small aggregates (9-25 mu m) 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.

• 出版日期2016-8