Interaction of viper venom serine peptidases with thrombin receptors on human platelets

被引:52
|
作者
Santos, BF
Serrano, SMT
Kuliopulos, A
Niewiarowski, S [1 ]
机构
[1] Temple Univ, Sch Med, Dept Physiol, Philadelphia, PA 19140 USA
[2] Inst Butantan, Sao Paulo, Brazil
[3] Temple Univ, Sch Med, Sol Sherry Thrombosis Res Ctr, Philadelphia, PA 19140 USA
[4] Tufts Univ, Sch Med, Boston, MA 02111 USA
关键词
thrombin receptor; protease activated receptor; platelet activation; viper venom protease; calcium mobilization; heparin; hirudin; thrombomodulin;
D O I
10.1016/S0014-5793(00)01803-2
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 serine peptidases, thrombocytin and PA-BJ, isolated from the venom of Bothrops atrox and Bothrops jararaca, respectively, induce platelet aggregation and granule secretion without clotting fibrinogen, The specific platelet aggregation activity of each enzyme was about 15 times lower than that of thrombin, This activity was blocked by monoclonal antibodies recognizing protease activated receptor 1 (PAR1) and by heparin, but not by hirudin nor thrombomodulin, Both enzymes induced calcium mobilization in platelets and desensitized platelets to the action of thrombin and the SFLLRN peptide. We compared the effect of thrombin, PA-BJ, and thrombocytin on the degradation of the soluble N-terminal domain of the PAR1 receptor. The major cleavage site by thrombin and both viper enzymes was Arg41-Ser42. In addition, a rapid cleavage of the peptide bond at Arg46-Asn47 by the viper enzymes was observed, resulting in the inactivation of the tethered ligand, PA-BJ and thrombocytin both cleaved at 41-42 and 46-47 peptide bonds, and fragment 42-103 disappeared rapidly. Both viper enzymes caused calcium mobilization in fibroblasts transfected with PAR4 and desensitized these cells to the thrombin action. In conclusion, both PAR1 and PAR4 mediate the effect of viper venom serine peptidases on platelets. (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
引用
收藏
页码:199 / 202
页数:4
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