Rhinocetin, a Venom-derived Integrin-specific Antagonist Inhibits Collagen-induced Platelet and Endothelial Cell Functions.

Vaiyapuri, Sakthivel, Hutchinson, E Gail, Ali, Marfoua S, Dannoura, Abeer, Stanley, Ronald G, Harrison, Robert, Bicknell, Andrew B and Gibbins, Jonathan M (2012) 'Rhinocetin, a Venom-derived Integrin-specific Antagonist Inhibits Collagen-induced Platelet and Endothelial Cell Functions.'. The Journal of Biological Chemistry, Vol 287, Issue 31, pp. 26235-26244.

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Abstract

Snaclecs are small non-enzymatic proteins present in viper venoms reported to modulate hemostasis of victims through effects on platelets, vascular endothelial, and smooth muscle cells. In this study, we have isolated and functionally characterized a snaclec that we named "rhinocetin" from the venom of West African gaboon viper, Bitis gabonica rhinoceros. Rhinocetin was shown to comprise α and β chains with the molecular masses of 13.5 and 13 kDa, respectively. Sequence and immunoblot analysis of rhinocetin confirmed this to be a novel snaclec. Rhinocetin inhibited collagen-stimulated activation of human platelets in a dose-dependent manner but displayed no inhibitory effects on glycoprotein VI (collagen receptor) selective agonist, CRP-XL-, ADP-, or thrombin-induced platelet activation. Rhinocetin antagonized the binding of monoclonal antibodies against the α2 subunit of integrin α2β1 to platelets and coimmunoprecipitation analysis confirmed integrin α2β1 as a target for this venom protein. Rhinocetin inhibited a range of collagen-induced platelet functions such as fibrinogen binding, calcium mobilization, granule secretion, aggregation, and thrombus formation. It also inhibited integrin α2β1-dependent functions of human endothelial cells. Together, our data suggest rhinocetin to be a modulator of integrin α2β1 function and thus may provide valuable insights into the role of this integrin in physiological and pathophysiological scenarios, including hemostasis, thrombosis, and envenomation.

Item Type:	Article
Subjects:	QU Biochemistry > Cells and Genetics > QU 375 Cell physiology QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 630 Toxins. Antitoxins WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 300 Blood platelets WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 310 Mechanism of blood coagulation. Hemostatis
Faculty: Department:	Groups (2002 - 2012) > Molecular & Biochemical Parasitology Group
Digital Object Identifer (DOI):	https://doi.org/10.1074/jbc.M112.381483
Depositing User:	Mary Creegan
Date Deposited:	05 Apr 2013 10:53
Last Modified:	06 Feb 2018 13:05
URI:	https://archive.lstmed.ac.uk/id/eprint/3262

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