KRDS, A NEW PEPTIDE DERIVED FROM HUMAN LACTOTRANSFERRIN, INHIBITS PLATELET-AGGREGATION AND RELEASE REACTION

被引:55
作者
MAZOYER, E
LEVYTOLEDANO, S
RENDU, F
HERMANT, L
LU, H
FIAT, AM
JOLLES, P
CAEN, J
机构
[1] HOP LARIBOISIERE,INSERM,U150,F-75475 PARIS 10,FRANCE
[2] HOP LARIBOISIERE,CNRS,UA 334,F-75475 PARIS 10,FRANCE
[3] UNIV PARIS 07,CNRS,UA 1188,PROT LAB,F-75221 PARIS 05,FRANCE
来源
EUROPEAN JOURNAL OF BIOCHEMISTRY | 1990年 / 194卷 / 01期
关键词
D O I
10.1111/j.1432-1033.1990.tb19424.x
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
KRDS (Lys‐Arg‐Asp‐Ser), a tetrapeptide from human lactotransferrin, was tested in vitro on human platelet function, and its effects were compared to those of RGDS, a tetrapeptide from human fibrinogen. Both peptides had a high probability of initiating a β‐turn and were highly hydrophilic. KRDS inhibited ADP‐induced platelet aggregation [median inhibitory concentration (IC50) 350 μM] and fibrinogen binding (IC50 360 μM) to a lesser extent than RGDS (IC50 75 μM and 20 μM, respectively). Different from RGDS, thrombin‐induced serotonin release was inhibited by KRDS (750 μM) on normal platelets (55 ± 10%) and type I Glanzmann's thrombasthenia platelets (43%± 1). However, KRDS had no effect on cytoplasmic Ca2+ mobilization, inositol phospholipid metabolism or protein phosphorylation (myosin light chain P20 and P43). In contrast to RGDS, KRDS does not inhibit the binding of monoclonal antibody PAC‐1 to activated platelets. KRDS and RGDS inhibited 4β‐phorbol‐12‐myristate‐13‐acetate (PMA)‐induced aggregation and fibrinogen binding, while proteins were normally phosphorylated. Thus, the tetrapeptide KRDS is (a) an inhibitor of serotonin release by a mechanism independent of protein phosphorylation and (b) an inhibitor of fibrinogen binding and, hence, aggregation by a mechanism that may not necessarily involve its direct binding to the glycoprotein IIb‐IIIa‐complex. Copyright © 1990, Wiley Blackwell. All rights reserved
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页码:43 / 49
页数:7
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