Release of Plasminogen Activator by Batroxobin

Klöcking, H.-P.; Hoffmann, A; Markwardt, Fritz

doi:10.1159/000215749

Cited by 7 publications

(5 citation statements)

References 6 publications

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“…Our results showed that patients with systemic bleeding presented increased levels of FDP, as well as decreased levels of plasminogen and alpha 2-antiplasmin, when compared to those without bleeding. B. atrox venom could be acting directly on fibrin and fibrinogen resulting in the generation of fibrinolysis products, and indirectly inducing the release of tissue plasminogen activator [ 6 , 15 , 38 , 39 ]. Also, the capacity of B. atrox venom to induce factor XIII activation [ 14 ], and intravascular thrombin generation [ 30 ] can contribute to the formation of intravascular cross-linked fibrin polymer and D-dimer.…”

Section: Discussionmentioning

confidence: 99%

Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor

Oliveira

Alves

Santos

et al. 2020

Toxins

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Bleeding is a common hemostatic disorder that occurs in Bothrops envenomations. We evaluated the changes in coagulation, fibrinolysis components, and platelets in Bothrops atrox envenomations with bleeding. This is an observational study with B. atrox snakebite patients (n = 100) treated in Manaus, Brazilian Amazon. Bleeding was recorded on admission and during hospitalization. We found that the platelet count in our patients presented a weak correlation to tissue factor, factor II, and plasminogen. Tissue factor presented weak correlation to factor V, II, D-dimer, plasminogen, alpha 2-antiplasmin, and moderate correlation to fibrinogen and fibrin/fibrinogen degradation product (FDP). Patients with systemic bleeding (n = 20) presented low levels of factor V, II, fibrinogen, plasminogen, and alpha 2-antiplasmin, and high levels of tissue factor and FDP compared to those without bleeding. Patients with only local bleeding (n = 41) and without bleeding showed similar levels of hemostatic factors. Thrombocytopenia was observed mainly in patients with systemic bleeding and increased levels of serum venom. No association was found between venom levels and systemic bleeding, or between venom levels and clinical severity of envenomation. This is the first report that shows the participation of the extrinsic coagulation pathway in the consumption coagulopathy of B. atrox envenomations with systemic bleeding due to tissue factor release.

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Section: Discussionmentioning

confidence: 99%

Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor

Oliveira

Alves

Santos

et al. 2020

Toxins

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“…Batroxobin, the TLE from B. moojeni venom, has been reported to cause a dosedependent increase in the release of t-PA from an isolated perfused pig ear preparation [84]. In an additional report, a TLE habutoxin from Trimeresurus flavoviridis venom stimulated bovine pulmonary artery endothelial cells to release increased levels of u-PA and Plg activator inhibitor (PAI) [85].…”

Section: Snake Venom Plasminogen Activators (Pas): Structural and Biomentioning

confidence: 99%

Proteases from South American Snake Venoms Affecting Fibrinolysis

Sanchez¹,

Swenson

2007

CPA

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Venoms of the viperidae (vipers and pit vipers) snakes are rich sources of proteinases which render fibrinogen incoagulable and solubilize fibrin. Many of these compounds have profound effects (stimulating or inhibiting) on the hemostatic mechanism, including, blood coagulation cascade, fibrinolysis, hypotension, vascular integrity and platelet function. The lethality of a venom often appears to be due to the combined action of several of these components, but severe consequences are frequently connected with hemostatic disorders. Viperid snake bite accidents in human and other large animals are characterized by localized or generalized bleeding and or thrombotic sequelae. This review is focused on the structural properties and features of a number of South American snake venom enzymes possessing clearly defined (pro)fibrinolytic activity. Under physiological conditions the venom proteins active on the plasminogen/fibrinolytic system can be grouped into two main categories: 1) direct-acting fibrinolytic endoproteinases which are related in amino acid sequence to the major family of metalloproteinases known as the metzincins. The members of this group are zinccontaining metalloproteinases (SVMPs) varying in size from 20 to 100 kDa and often more than one example is present in the same venom. 2) serine proteinases which specifically activate plasminogen into plasmin, and contain at least one catalytic domain structurally similar to trypsin. A number of these proteinases have been isolated and their mechanism of action established. Both direct and indirect endoproteinases on their own are practically nontoxic; however, they may act synergistically with other factors aggravating their toxic effects. Moreover, these proteinases are characterized by a relatively high degree of substrate specificity and resistance to physiological inhibitors. Indeed, some of these venom components are thought to hold promise as agents for medical applications in the field of thrombosis and diagnosis, or to hold the key for the design of pharmaceuticals.

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“…Experimental data of coagulation parameters analysis demonstrated that recombinant batroxobin has no significant influence on other coagulation factors. Snake venom thrombin-like enzymes such as batroxobin, crotalase and ancrod were known to have not only potent procoagulant activities but also defibrinogenating activities, which are associated with the reduction of fibrinogen level in plasma by clearing converted fibrinogen and enhancing fibrinolytic activity [9,10,[32][33][34]. Recombinant and native batroxobins also decreased fibrinogen concentration in rat plasma (Fig.…”

Section: Effects Of Recombinant Batroxobin On Coagulation Parametersmentioning

confidence: 99%

Functional characterization of recombinant batroxobin, a snake venom thrombin‐like enzyme, expressed from Pichia pastoris

et al. 2004

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A thrombin-like enzyme of Bothrops atrox moojeni venom, batroxobin, specifically cleaves fibrinogen a chain, resulting in the formation of non-crosslinked fibrin clots. The cDNA encoding batroxobin was cloned, expressed in Pichia pastoris and the molecular function of purified recombinant protein was also characterized. The recombinant batroxobin had an apparent molecular weight of 33 kDa by SDS-PAGE analysis and biochemical activities similar to those of native batroxobin. The purified recombinant protein strongly converted fibrinogen into fibrin clot in vitro, and shortened bleeding time and whole blood coagulation time in vivo. However, it did not make any considerable alterations on other blood coagulation factors. Several lines of experimental evidence in this study suggest that the recombinant batroxobin is a potent procoagulant agent.

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Release of Plasminogen Activator by Batroxobin

Abstract: In the isolated perfused pig ear, batroxobin caused a dose-dependent increase in the release of plasminogen activator. The activator-releasing effect required the presence of the active enzyme. The activator released was of the tissue-type.

Cited by 7 publications

References 6 publications

Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor

Bleeding Disorders in Bothrops atrox Envenomations in the Brazilian Amazon: Participation of Hemostatic Factors and the Impact of Tissue Factor

Proteases from South American Snake Venoms Affecting Fibrinolysis

Functional characterization of recombinant batroxobin, a snake venom thrombin‐like enzyme, expressed from Pichia pastoris

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