Departamento de Biologia Molecular, CCEN, UFPB, João Pessoa, PB, Brazil.
Departamento de Física e Biofísica, Instituto de Biociências, UNESP, Botucatu, SP, Brazil.
Int J Biol Macromol. 2019 Jun 15;131:127-133. doi: 10.1016/j.ijbiomac.2019.03.059. Epub 2019 Mar 10.
Among the activities triggered by Crotalus durissus terrificus snake venom, coagulation is intriguing and contradictory since the venom contains both coagulant and anticoagulant precursor proteins. This work describes the in vitro effects of crude venom and purified proteins from snake Crotalus durissus terrificus as they affect coagulation factors of clotting pathways. Coagulant and/or anticoagulant activities of crude venom, and purified proteins were all analyzed directly in human plasma. Clots formed by crude venom and Gyroxin presented as flexible hyaline masses in punctiform distribution. Clot formation time evaluation of isolated proteins with PT and APTT assays made it possible to infer that these proteins interfere in all coagulation pathways. However, regarding ophidism by C. d. terrificus, Gyroxin acts directly, breaking down fibrinogen to fibrin and increasing the amount plasminogen activator, which results in the formation of thrombi. Crotoxin complex, Crotoxin A and Crotoxin B proteins can act in prothrombinase complex formation; Crotoxin B can inhibit prothrombinase complex formation by direct interaction with Factor Xa. Crotamine interacts with negatively charged regions of differing coagulation factors in all coagulation pathways, and possesses a whole set of activities causing dysfunction, activation and/or inhibition of natural anticoagulants and disturbing hemostasis.
响尾蛇蛇毒引发的诸多活动中,凝血作用非常有趣,但也存在矛盾,因为蛇毒中既含有促凝蛋白,也含有抗凝蛋白前体。本研究描述了响尾蛇蛇毒粗提物和纯化蛋白对凝血途径中凝血因子的体外影响。粗提物和纯化蛋白的促凝和/或抗凝活性均直接在人血浆中进行分析。粗提物和 Gyroxin 形成的血栓呈点状分布的柔软透明团块。PT 和 APTT 测定法对分离蛋白的血栓形成时间评估使我们能够推断这些蛋白干扰所有凝血途径。然而,对于响尾蛇 C. d. terrificus 的蛇伤,Gyroxin 直接作用,将纤维蛋白原分解为纤维蛋白,并增加纤溶酶原激活物的量,导致血栓形成。Crotoxin 复合物、Crotoxin A 和 Crotoxin B 蛋白可在凝血酶原酶复合物形成中发挥作用;Crotoxin B 可通过与 Xa 因子直接相互作用抑制凝血酶原酶复合物的形成。Crotamine 与所有凝血途径中不同凝血因子的带负电荷区域相互作用,具有一系列导致功能障碍、激活和/或抑制天然抗凝剂以及扰乱止血的活性。