A novel family of RGD-containing disintegrins (Tablysin-15) from the salivary gland of the horsefly Tabanus yao targets αIIbβ3 or αVβ3 and inhibits platelet aggregation and angiogenesis
文献类型：期刊论文
| 作者 | Ma DY1; Xu XQ2; Andersen JF2; Wang YP1; Tokumasu F3; Ribeiro JMC2; Francischetti IMB[*]2; Lai R[*]1; An S1,4; Liu H1 |
| 刊名 | THROMBOSIS AND HAEMOSTASIS
 |
| 出版日期 | 2011 |
| 卷号 | 105期号:6页码:1032-1045 |
| 关键词 | Haematophagy blood-sucking disintegrin thrombosis sialogenins |
| 其他题名 | ifrancischetti@niaid.nih.gov; rlai@mail.kiz.ac.cn |
| 通讯作者 | ifrancischetti@niaid.nih.gov |
| 合作状况 | 其它 |
| 英文摘要 | A novel family of RGD-containing molecules (Tablysin-15) has been molecularly characterised from the salivary gland of the haematophagous horsefly Tabanus yao. Tablysin-15 does not share primary sequence homology to any disintegrin discovered so far, and displays an RGD motif in the N-terminus of the molecule. It is also distinct from disintegrins from Viperidae since its mature form is not released from a metalloproteinase precursor. Tablysin-15 exhibits high affinity binding for platelet alpha(IIb)beta(3) and endothelial cell alpha(V)beta(3) integrins, but not for alpha(5)beta(1) or alpha(2)beta(1). Accordingly, it blocks endothelial cell adhesion to vitronectin (IC50 similar to 1 nM) and marginally to fibronectin (IC50 similar to 1 mu M), but not to collagen. It also inhibits fibroblast growth factor (FGF)-induced endothelial cell proliferation, and attenuates tube formation in vitro. In platelets, Tablysin-15 inhibits aggregation induced by collagen, ADP and convulxin, and prevents static platelet adhesion to immobilised fibrinogen. In addition, solid-phase assays and flow cytometry demonstrates that a(IIb)beta(3) binds to Tablysin-15. Moreover, immobilised Tablysin-15 supports platelet adhesion by a mechanism which was blocked by anti-integrin a(IIb)beta(3) monoclonal antibody (e.g. abciximab) or by EDTA. Furthermore, Tablysin-15 dose-dependently attenuates thrombus formation to collagen under flow. Consistent with these findings, Tablysin-15 displays antithrombotic properties in vivo suggesting that it is a useful tool to block a(IIb)beta(3), or as a prototype to develop antithrombotics. The RGD motif in the unique sequence of Tablysin-15 represents a novel template for studying the structure-function relationship of the disintegrin family of inhibitors. |
| 收录类别 | SCI |
| 资助信息 | This work was supported by the Chinese National Natural Science Foundation (30830021 and 30800185), the Chinese Ministry of Science and Technology (2010CB529800) and the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/9595]  |
| 专题 | 昆明动物研究所_动物毒素室 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China 2.Vector Biology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 3.Biochemical and Biophysical Parasitology Section, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA 4.School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, China |
| 推荐引用方式 GB/T 7714 | Ma DY,Xu XQ,Andersen JF,et al. A novel family of RGD-containing disintegrins (Tablysin-15) from the salivary gland of the horsefly Tabanus yao targets αIIbβ3 or αVβ3 and inhibits platelet aggregation and angiogenesis[J]. THROMBOSIS AND HAEMOSTASIS,2011,105(6):1032-1045. |
| APA | Ma DY.,Xu XQ.,Andersen JF.,Wang YP.,Tokumasu F.,...&Yang XN.(2011).A novel family of RGD-containing disintegrins (Tablysin-15) from the salivary gland of the horsefly Tabanus yao targets αIIbβ3 or αVβ3 and inhibits platelet aggregation and angiogenesis.THROMBOSIS AND HAEMOSTASIS,105(6),1032-1045. |
| MLA | Ma DY,et al."A novel family of RGD-containing disintegrins (Tablysin-15) from the salivary gland of the horsefly Tabanus yao targets αIIbβ3 or αVβ3 and inhibits platelet aggregation and angiogenesis".THROMBOSIS AND HAEMOSTASIS 105.6(2011):1032-1045. |
入库方式： OAI收割
来源：昆明动物研究所
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