Hemolytic and anticoagulant study of the neurotoxin vipoxin and its components--basic phospholipase A2 and an acidic inhibitor.
In the present study, we demonstrate for the first time that the potent neurotoxin vipoxin from the venom of Vipera ammodytes meridionalis exhibits hemolytic and anticoagulant properties. By investigating the effects of phospholipids and calcium ions on hemolysis, we established that the phospholipase A2 (PLA2) enzyme activity is responsible for the hemolytic properties. This was confirmed by chemical modification of the PLA2 active-site histidine residue with p-bromophenacylbromide. Applying different clotting assays, we show that the PLA2 is a weakly anticoagulant enzyme, which affects intrinsic tenase complex by the hydrolysis of procoagulant phospholipids, rather than by nonenzymatic mechanisms (binding to specific coagulation factors). The whole complex--vipoxin--does not affect the coagulation system.
Laboratory of Biocoordination and Bioanalytical Chemistry, Department of Analytical Chemistry, Faculty of Chemistry, Sofia University, J. Bourchier Ave. 1, 1164 Sofia, Bulgaria. vatanasov@chem.uni-sofia.bg
V N
VN
Atanasov
D
D
Danchev
M
M
Mitewa
S
S
Petrova
D000818:Animals; D000925:Anticoagulants / Q000378:metabolism / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000378:metabolism*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D010314:Partial Thromboplastin Time; D054467:Phospholipases A2 / Q000378:metabolism*; D011517:Prothrombin Time; D013918:Thrombin Time; D014757:Viper Venoms / Q000378:metabolism / Q000494:pharmacology*; D017819:Viperidae / Q000378:metabolism
D000925:Anticoagulants; D004791:Enzyme Inhibitors; D014757:Viper Venoms; C033134:vipoxin; D054467:Phospholipases A2