磷酸肌醇3激酶在癌促凝剂刺激的血小板与纤维蛋白原黏附中的作用

Role of phosphoinositide 3-kinase in adhesion of platelets to fibrinogen stimulated by cancer procoagulant.

作者信息

Olas B, Wachowicz B, Mielicki W P

机构信息

Department of General Biochemistry, Institute of Biochemistry, University of Łódź, Banacha 12/16, 90-237 Łódź, Poland.

出版信息

Platelets. 2001 Nov;12(7):431-5. doi: 10.1080/09537100120085469.

DOI:10.1080/09537100120085469

PMID:11674861

Abstract

Cancer procoagulant, cysteine proteinase (CP; EC 3.4.22.26) activates factor X and functions in the absence of factor VII. CP may also change the platelet function. It induces an increase of platelet adhesion to collagen and fibrinogen. Using wortmannin--the inhibitor of phosphoinositide 3-kinase (PI 3-K)--we studied the role of this enzyme in the action of cancer procoagulant on blood platelet adhesion in vitro. Wortmannin (25, 50 and 100 nM, 30 min, 37 degrees C) caused a reduction of platelet adhesion to fibrinogen (P<0.01) when blood platelets were stimulated by both 0.2 U/ml thrombin (IC(50)approximately 75 nM) and by 1 microM ADP (IC(50)approximately 60 nM). We observed that after CP treatment the adhesion of thrombin-activated and ADP-stimulated platelets to fibrinogen was augmented. The potentiated by CP adhesion of activated platelets to fibrinogen was reduced after preincubation of platelets with wortmannin (50 nM, 30 min, 37 degrees C). We conclude that in adhesion of platelets to fibrinogen stimulated by CP PI 3-K take place.

摘要

癌促凝物质，一种半胱氨酸蛋白酶（CP；EC 3.4.22.26）可激活因子X，且在无因子VII的情况下发挥作用。CP也可能改变血小板功能。它可诱导血小板与胶原蛋白和纤维蛋白原的黏附增加。我们使用渥曼青霉素（一种磷酸肌醇3激酶（PI 3-K）抑制剂）研究了该酶在癌促凝物质体外作用于血小板黏附过程中的作用。当血小板分别受到0.2 U/ml凝血酶（IC50约为75 nM）和1 μM ADP（IC50约为60 nM）刺激时，渥曼青霉素（25、50和100 nM，37℃处理30分钟）可导致血小板与纤维蛋白原的黏附减少（P<0.01）。我们观察到，CP处理后，凝血酶激活的和ADP刺激的血小板与纤维蛋白原的黏附增强。在用渥曼青霉素（50 nM，37℃处理30分钟）预孵育血小板后，CP增强的活化血小板与纤维蛋白原的黏附减少。我们得出结论，在CP刺激的血小板与纤维蛋白原的黏附过程中，PI 3-K发挥了作用。