Mechanism of collagen-induced release of 5-HT, PDGF-AB and sCD40L from human platelets: Role of HSP27 phosphorylation via p44/p42 MAPK

被引:18
作者
Kato, Hisaaki [1 ,2 ]
Adachi, Seiji [2 ]
Doi, Tomoaki [1 ,2 ]
Matsushima-Nishiwaki, Rie [2 ]
Minamitani, Chiho [2 ,3 ]
Akamatsu, Shigeru [4 ]
Enomoto, Yukiko [5 ]
Tokuda, Haruhiko [2 ,6 ]
Otsuka, Takanobu [3 ]
Iwama, Toru [5 ]
Kozawa, Osamu [2 ]
Ogura, Shinji [1 ]
机构
[1] Gifu Univ, Grad Sch Med, Dept Emergency & Disaster Med, Gifu, Japan
[2] Gifu Univ, Grad Sch Med, Dept Pharmacol, Gifu, Japan
[3] Nagoya City Univ, Grad Sch Med Sci, Dept Orthoped Surg, Nagoya, Aichi, Japan
[4] Matsunami Gen Hosp, Dept Intens Care Med, Gifu, Japan
[5] Gifu Univ, Grad Sch Med, Dept Neurosurg, Gifu, Japan
[6] Natl Hosp Geriatr Med, Natl Ctr Geriatr & Gerontol, Dept Clin Lab, Obu, Japan
关键词
HSP27; platelet; collagen; release; 5-HT; PDGF-AB; sCD40L; ACTIVATED PROTEIN-KINASE; HEAT-SHOCK PROTEINS; ALPHA-B-CRYSTALLIN; ACTIN POLYMERIZATION; STRESS; INHIBITOR; MODULATION; DYNAMICS; PATHWAY;
D O I
10.1016/j.thromres.2009.12.003
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Collagen plays a crucial role in hemostasis and thrombosis by activating platelets and reportedly induces the phosphorylation of heat shock protein (HSP) 27 in human platelets. However, the exact role of HSP27 phosphorylation in human platelets has not yet been clarified. In the present study, we investigated the mechanism of collagen-induced HSP27 phosphorylation and the role in human platelets. The collagen-effect on the phospholylation of HSP27 was dose-dependent in the range between 0.03 and 1.0 mu g/ml. The phosphorylation of p44/p42 mitogen-activated protein kinase (MAPK) was also stimulated by collagen. PD98059, a specific inhibitor of MAPK kinase (MEK1/2), reduced collagen-induced HSP27 phosphorylation as well as p44/p42 MAPK phosphorylation. PD98059 significantly suppressed collagen-induced releases of serotonin (5-HT), platelet-derived growth factor (PDGF)-AB and soluble CD40 ligand (sCD40L) while it had little effect on the platelet aggregation. These results strongly suggest that the collagen-induced phosphorylation of HSP27 via p44/p42 MAPK is sufficient for releases of 5-HT, PDGF-AB and sCD40L from human platelets. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:39 / 43
页数:5
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