Characterization of 'basparin A,' a prothrombin-activating metalloproteinase, from the venom of the snake Bothrops asper that inhibits platelet aggregation and induces defibrination and thrombosis

Loria, G. D., Rucavado, A., Kamiguti, A. S., Theakston, R.David G., Fox, J. W., Alape, A. and Gutierrez, J. M. (2003) 'Characterization of 'basparin A,' a prothrombin-activating metalloproteinase, from the venom of the snake Bothrops asper that inhibits platelet aggregation and induces defibrination and thrombosis'. Archives of Biochemistry and Biophysics, Vol 418, Issue 1, pp. 13-24.

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Abstract

A prothrombin activator, named 'basparin A,' was isolated from the venom of the crotaline snake Bothrops asper, the species responsible for the majority of snakebite cases in Central America. It is an acidic (pI 5.4), 70kDa, single chain P-III metalloproteinase comprising, in addition to the metalloproteinase domain, disintegrin-like, and high-cysteine domains. Basparin A is a glycoprotein displaying immunological cross-reactivity with BaH1, a P-III hemorrhagic metalloproteinase isolated from the same venom. It activates prothrombin through the formation of meizothrombin, without requiring additional cofactors; it is, therefore, a class A snake venom prothrombin activator. In contrast with most venom metalloproteinases, it does not degrade components of the extracellular matrix. Apart from its clotting activity, basparin A inhibits collagen-dependent platelet aggregation in vitro, an effect that does not depend on proteolytic activity. Clotting activity on human plasma is not abrogated by the plasma proteinase inhibitors alpha(2) macroglobulin and murinoglobulin, whereas activity is completely inhibited by Costa Rican polyvalent (Crotalinae) anti-venom. Basparin A does not induce local tissue alterations, such as hemorrhage, myonecrosis, and edema, in mice. Moreover, it does not induce systemic hemorrhage, thrombocytopenia nor prolongation of the bleeding time following intravenous administration. At low doses, the only observed effect induced by basparin A, when injected intravenously or intramuscularly into mice, is defibrin(ogen)ation. At higher doses, intravenous administration resulted in sudden death due to numerous occluding thrombi in pulmonary vessels. Basparin A is likely to play an important role in the coagulopathy associated with B. asper envenoming. (C) 2003 Elsevier Inc. All rights reserved.

Item Type:	Article
Uncontrolled Keywords:	Bothrops asper venom; Prothrombin activator; Metalloproteinase; Defibrination; Platelet aggregation inhibition
Subjects:	QY Clinical Pathology > Blood. Blood Chemistry > QY 410 Coagulation WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1016/s0003-9861(03)00385-0
Depositing User:	Ms Julia Martin
Date Deposited:	31 Aug 2012 13:06
Last Modified:	06 Feb 2018 13:04
URI:	https://archive.lstmed.ac.uk/id/eprint/2601

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