Role of cAMP-dependent protein kinase in the regulation of platelet procoagulant activity

被引：22

作者：

Yan, Rong ^{[1
]}

Wang, Zhicheng ^{[1
]}

Yuan, Yanhong ^{[1
]}

Cheng, Hong ^{[1
]}

Dai, Kesheng ^{[1
]}

机构：

[1] Beijing Univ Aeronaut & Astronaut, Dept Biol Sci & Technol, Beijing 100083, Peoples R China

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2009年 / 485卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Platelet; Microparticle; Phosphatidylserine; cAMP-dependent protein kinase (PKA); Calpain; GLYCOPROTEIN-IB-BETA; MICROPARTICLE FORMATION; PLASMA-MEMBRANE; AMINOPHOSPHOLIPID EXPOSURE; SELECTIN EXPRESSION; THROMBIN GENERATION; HIGH-SHEAR; PHOSPHORYLATION; ACTIVATION; CALPAIN;

D O I：

10.1016/j.abb.2009.02.014

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The membrane microparticle (MP) formation and phosphatidylserine (PS) exposure evoked by platelet activation provide Catalytic Surfaces for thrombin generation. Several reports have indicated the effects of cAMP-elevating agents on agonist-induced MP formation and PS exposure; however, the mechanism still remains Unclear. Here we show that inhibition of basal cyclic AMP-dependent protein kinase (PKA) activity incurred platelet MP formation and PS exposure. Pretreatment of platelets with cAMP-elevating agent, forskolin, abolished thrombin plus collagen-induced MP formation and PS exposure, and obviously decreased calcium ionophore-evoked MP shedding. Moreover, the inhibitory effects of forskolin on agonists-induced MP formation and PS exposure were reversed by the PKA inhibitor H89. PKA inhibitor-induced MP formation was dose-dependently inhibited by calpain inhibitor MDL28170. and forskolin abrogated thrombin Plus collagen-induced calpain activation. In conclusion, PKA plays key roles in the regulation of platelet MP formation and PS exposure. PKA-mediated MP shedding is dependent oil calpain activation. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：41 / 48

页数：8

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