Abstract
Biomolecules from Cerastes cerastes venom have been purified and characterized. Two phospholipases isolated from Cerastes cerastes venom share 51% of homology. CC2-PLA2 exhibits antiplatelet activity that blocks coagulation. CCSV-MPase, a non-hemorrhagic Zn2+-metalloproteinase, significantly reduced the plasmatic fibrinogen level and hydrolyzes only its Bβ chain. Serine proteinases such as RP34, afaâcytin and CC3-SPase hydrolyze the fibrinogen and are respectively α, αβ and αβ fibrinogenases. In deficient human plasma, afaâcytin replaces the missing factors VIII and IX, and activates purified human factor X into factor Xa. It releases serotonin from platelets and directly aggregates human (but not rabbit) blood platelets. RP34 proteinase also had no effect on both human and rabbit blood platelet aggregation. CC3-SPase revealed a pro-coagulant activity. However, the insolubility of the obtained clot indicates that CC3-SPase does not activate factor XIII. In addition, CC3-SPase clotting activity was carried out with human plasmas from volunteer patients deficient in clotting factors. Results showed that CC3-SPase shortens clotting time of plasma deficient in factors II and VII but with weaker clotting than normal plasma. The clotting time of plasma deficient in factor II is similar to that obtained with normal plasma; suggesting that CC3-SPase is able to replace both factors IIa and VII in the coagulation cascade and thus could be involved in the blood clotting process via an extrinsic pathway. These results imply that CC3-SPase and afaâcytin could repair hemostatic abnormalities and may replace some factors missing in pathological deficiency. Afaâcytin also exhibits α fibrinase property similar to a plasmin-like proteinase. Despite its thrombin-like characteristics, afaâcytin is not inhibited by plasmatic thrombin inhibitors. The procoagulant properties of afaâcytin might have potential clinical applications.
Highlights
Serine proteases and phospholipases A2 isolated from snake venoms act on the hemostatic system as procoagulants, anticoagulants, pro- or anti-platelet aggregants
Metalloproteinases can cause hemorrhage after accidental or experimental envenomation. Some of these metalloproteinases are directly involved in the clotting of blood as they can act on fibrinogen and/or fibrin; they are called in this case fibrino(geno)lytic metalloproteinases
Proteinases from Viperidae venoms are widely used as anticoagulants
Summary
Serine proteases and phospholipases A2 isolated from snake venoms act on the hemostatic system as procoagulants, anticoagulants, pro- or anti-platelet aggregants. These proteinases may be useful for investigating the mechanisms of blood coagulation and platelet aggregation [11,12] In addition to their beneficial effects, venom molecules are the cause of health problems after snake envenomation. Cerastes cerastes venom is a mixture of various proteins with broad biological and physiological activities; most of them are proteinases while some have been well characterized Most of these proteins act on blood coagulation, including PLA2, the thrombin-like enzymes. Coagulant and fibrinogenolytic activities of isolated molecules Fibrinogen is a glycoprotein of 340 kDa with three polypeptide chains; Aα (67 kDa), Bβ (50 kDa) and γ (43 kDa) linked by disulfide bonds It can be hydrolyzed by thrombin, producing fibrin components and fibrinopeptides. The crystal structure showed that the C-terminal region required for binding to FXa and CaM is highly exposed and accessible for interaction with receptor proteins in the monomeric and dimeric forms of ammodytoxin [45]
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