Antithrombin III suppresses ADP-induced platelet granule secretion: Inhibition of HSP27 phosphorylation

• Published in: Archives of biochemistry and biophysics Vol. 489; no. 1; pp. 62 - 67
• Main Authors: Doi, Tomoaki, Adachi, Seiji, Takai, Shinji, Matsushima-Nishiwaki, Rie, Kato, Hisaaki, Enomoto, Yukiko, Minamitani, Chiho, Otsuka, Takanobu, Tokuda, Haruhiko, Akamatsu, Shigeru, Iwama, Toru, Kozawa, Osamu, Ogura, Shinji
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2009
• Subjects: Adenosine Diphosphate - metabolism; Adenosine Diphosphate - pharmacology; ADP; Anticoagulants - pharmacology; Antithrombin; Antithrombin III - metabolism; Antithrombin III - pharmacology; Blood Platelets - secretion; CD40 Ligand - secretion; Enzyme Inhibitors - pharmacology; Flavonoids - pharmacology; HSP27 Heat-Shock Proteins - metabolism; Humans; Imidazoles - pharmacology; Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors; Mitogen-Activated Protein Kinase 3 - metabolism; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; PDGF-AB; Phosphorylation - drug effects; Platelet; Platelet-Derived Growth Factor - secretion; Pyridines - pharmacology; sCD40L; Secretory Vesicles - secretion; Serotonin; Serotonin - secretion; sCD40L; Platelet; Serotonin; Antithrombin; ADP; PDGF-AB
• ISSN: 0003-9861; 1096-0384
• DOI: 10.1016/j.abb.2009.07.009

Antithrombin III (AT-III), an anti-coagulant, has recently been reported to directly affect human platelet functions. However, the exact mechanism of AT-III in platelets remains to be clarified. We have previously shown that adenosine diphosphate (ADP)-induced phosphorylation of heat shock protein 27 (HSP27) via p44/p42 mitogen-activated protein kinase (MAPK) and p38 MAPK is correlated with platelet granule secretion. In the present study, we investigated the relationship between AT-III and the ADP-induced platelet granule secretion. The ADP-induced secretion of platelet-derived growth factor (PDGF)-AB and serotonin (5-HT) were significantly suppressed by AT-III. The ADP-induced soluble CD40 ligand (sCD40L) release was inhibited by either PD98059, a MEK inhibitor, or SB203580, a p38 MAPK inhibitor. AT-III also inhibited the sCD40L release. AT-III markedly attenuated the ADP-induced phosphorylation levels of p44/p42 MAPK and p38 MAPK. Furthermore, the ADP-induced HSP27 phosphorylation was suppressed by AT-III. These results strongly suggest that AT-III directly acts on platelets and suppresses ADP-induced platelet granule secretion due to inhibiting HSP27 phosphorylation via p44/p42 MAPK and p38 MAPK.