Title: Anti-hemostatic effects of the recombinant DisBa-01, a novel RGD-containing disintegrin from Bothrops alternans
Authors: Kauskot, Alexandre ×
Cominetti, Marcia R
Ramos, Oscar H P
Bechyne, Iga
Renard, Jean-Marie
Hoylaerts, Marc
Crepin, Michel
Legrand, Chantal
Selistre-de-Araujo, Heloisa S
Bonnefoy, Arnaud #
Issue Date: May-2008
Publisher: Frontiers in Bioscience Publications
Series Title: Frontiers in Bioscience vol:13 pages:6604-6616
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 alpha(v)beta3 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.
ISSN: 1093-9946
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
× corresponding author
# (joint) last author

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