IMR Press / FBL / Volume 13 / Issue 17 / DOI: 10.2741/3176

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Hemostatic effects of recombinant DisBa-01, a disintegrin from Bothrops alternatus
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1 INSERM U553, Paris, F-75475, France
2 Universite Paris 7, IFR 105, Paris, F-75475, France
3 Department of Ciencias Fisiologicas, Universidade Federal de Sao Carlos, Sao Carlos, Brasil
4 Center for Molecular and Vascular Biology, University of Leuven, B-3000, Leuven, Belgium
5 Universite Paris 13, CNRS UMR 7033, Bobigny, F-93000, France
6 INSERM U743, Centre de Recherche du Centre Hospitalier de l’Universite de Montreal-Saint-Luc, Montreal QC, H2X1P1, Canada
7 Centre de Recherche de l’Institut de Cardiologie de Montreal, Montreal QC, H1T1C8, Canada

*Author to whom correspondence should be addressed.

Academic Editor: Xinjie Lu

Front. Biosci. (Landmark Ed) 2008, 13(17), 6604–6616; https://doi.org/10.2741/3176
Published: 1 May 2008
(This article belongs to the Special Issue Disintegrins in health and disease)
Abstract

A monomeric RGD-disintegrin was recently identified from a cDNA library from the venom gland of Bothrops alternatus. The corresponding 12 kDa-recombinant protein, DisBa-01, specifically interacted with alphavbeta3 integrin and displayed potent anti-metastatic and anti-angiogenic properties. Here, the interaction of DisBa-01 with platelet alphaIIb beta3 integrin and its effects on hemostasis and thrombosis were investigated. DisBa-01 bound to Chinese Hamster Ovary (CHO) cells expressing beta3 or alphaIIb beta3 and promoted their adhesion and the adhesion of resting platelets onto glass coverslips. The disintegrin inhibited the binding of FITC-fibrinogen and FITC-PAC-1 to ADP-stimulated platelets and inhibited ADP-, TRAP- and collagen-induced aggregation of murine, rabbit or human platelets. In a flow chamber assay, DisBa-01 inhibited and reverted platelet adhesion to immobilized fibrinogen. DisBa-01 inhibited the phosphorylation of FAK following platelet activation. The intravenous injection of DisBa-01 in C57Bl6/j mice, prolonged tail bleeding time as well as thrombotic occlusion time in mesenteric venules and arterioles following vessel injury with FeCl3. In conclusion, DisBa-01 antagonizes the platelet alphaIIb beta3 integrin and potently inhibits thrombosis.

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