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从哥伦比亚响尾蛇毒液中分离的纤维蛋白溶酶金属蛋白酶(哥伦比亚酶)的功能表征。

Functional characterization of fibrinolytic metalloproteinases (colombienases) isolated from Bothrops colombiensis venom.

机构信息

Laboratorio de Inmunoquímica y Ultraestructura, Instituto Anatómico de la Universidad Central de Venezuela, Caracas, Venezuela.

出版信息

Toxicon. 2013 Nov;74:116-26. doi: 10.1016/j.toxicon.2013.07.025. Epub 2013 Aug 17.

DOI:10.1016/j.toxicon.2013.07.025
PMID:23958522
Abstract

UNLABELLED

Researchers trying to improve the safety and efficacy of fibrinolytic therapy have been isolating fibrinolytic enzymes from snake venoms. Two fibrinolytic enzymes, colombienases 1 and 2, with significant activity have been isolated from the venom of Bothrops colombiensis.

METHODS

The colombienases were characterized for various biological activities which include hemorrhagic, fibrinogenolytic, proteolytic, hemolytic, edematogenic and cytotoxic.

RESULTS

Colombienases directly acted on fibrin by degrading fibrinogen Aα and Bβ chains without activating the fibrinolytic system (plasminogen/plasmin), additionally colombienase-2 degraded fibrinogen γ chains as well as the fibronectin molecule. Laminin and type IV collagen were colombienases resistant. Gelatin-zymogram activity was present in B. colombiensis venom (BcV) bands between 64 and 148 kDa. All activities were abolished by metalloproteinases inhibitors. Both enzymes lacked hemorrhagic, hemolytic, cytotoxic, plasminogen activator and coagulant activities.

CONCLUSIONS

Both colombienases had direct fibrino(geno)lytic activity without other toxic side effects including in vivo hemorrhaging, which could be promising in terms of therapeutic potential as thrombolytic agents.

摘要

未加标签

研究人员试图提高纤维蛋白溶解疗法的安全性和有效性,一直在从蛇毒液中分离纤维蛋白溶解酶。从 Bothrops colombiensis 毒液中分离出两种具有显著活性的纤维蛋白溶解酶,即 colombienase 1 和 2。

方法

对 colombienases 的各种生物学活性进行了表征,包括出血性、纤维蛋白原水解酶活性、蛋白水解酶活性、溶血活性、水肿形成活性和细胞毒性。

结果

Colombienases 通过直接降解纤维蛋白原 Aα 和 Bβ 链而不激活纤维蛋白溶解系统(纤溶酶原/纤溶酶)作用于纤维蛋白,此外,colombienase-2 还降解纤维蛋白原 γ 链以及纤维连接蛋白分子。层粘连蛋白和 IV 型胶原蛋白是 colombienases 的抗性物质。明胶-酶谱活性存在于 B. colombiensis 毒液(BcV)64 至 148 kDa 的带中。所有活性均被金属蛋白酶抑制剂所抑制。两种酶均缺乏出血性、溶血活性、细胞毒性、纤溶酶原激活剂和凝血活性。

结论

两种 colombienases 均具有直接的纤维蛋白(原)溶解活性,而没有其他毒性副作用,包括体内出血,这在作为溶栓剂的治疗潜力方面可能具有前景。

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