A novel anti-platelet peptide (Z4A5) potential for glycoprotein IIb/IIIa inhibits platelet aggregation
| Autor: | Shu-Ting Ren, Yi-Ran Liao, Ying-Xue Li, Qiang Sun, Ya Wang, Xin-Liang Shen, Bing Wang, Hui Zhang |
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| Rok vydání: | 2012 |
| Předmět: |
Blood Platelets
Platelet Aggregation biology Fibrinogen binding Platelet Glycoprotein GPIIb-IIIa Complex Hematology Fibrinogen Molecular biology Umbilical vein Cell Line Adenosine diphosphate chemistry.chemical_compound Thrombin Fibrinolytic Agents chemistry Human Umbilical Vein Endothelial Cells biology.protein medicine Humans Vitronectin Platelet Glycoprotein IIb/IIIa Oligopeptides Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | Thrombosis Research. 129:e217-e222 |
| ISSN: | 0049-3848 |
| Popis: | Introduction Z4A5 is a novel peptide that inhibits platelet aggregation and formation of platelet thrombi, but the mechanism of its anti-platelet effects remains unknown. This study explores the anti-platelet effect and mechanism of Z4A5. Methods We investigated the anti-platelet activity of Z4A5 on platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA) and thrombin (TH) in human platelet-rich plasma (PRP). Fibrinogen and PAC-1 binding to glycoproteinIIb/IIIa (GPIIb/IIIa) were measured by flow cytometry. In addition, we investigated the integrin specificity of Z4A5 in attachment and detachment assays using human umbilical vein endothelial cells (HUVEC) and assessed the relative cell number using the MTT assay. Results In vitro, Z4A5 inhibited ADP-, AA- and TH-induced human platelet aggregation with IC50 values of 0.46 ± 0.05 μM (n = 10), 0.23 ± 0.05 μM (n = 10) and 0.21 ± 0.02 μM (n = 10), respectively. Z4A5 inhibited fibrinogen, and PAC-1 bound to platelet GPIIb/IIIa with IC50 values of 0.48 ± 0.07 μM (n = 8) and 0.63 ± 0.12 μM (n = 6), respectively. Z4A5 failed to inhibit αVβ3 integrin-mediated HUVEC attachment to vitronectin and did not cause any significant detachment of HUVEC monolayer when compared with the controls. Conclusions Z4A5 is a potential anti-platelet drug that inhibits fibrinogen binding to GPIIb/IIIa, but does not affect the structurally similar integrin αVβ3. |
| Databáze: | OpenAIRE |
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