Biochemical characterization and molecular cloning of a plasminogen activator proteinase (LV-PA) from bushmaster snake venom

Sanchez, Eládio Flores; Felicori, Liza; Chávez-Olortégui, Carlos; Magalhaes, Henrique B.P.; Hermogenes, Ana L.; Diniz, Marcelo V.; Junqueira-de-Azevedo, Inácio L.M.; Magalhães, Ana C.; Richardson, Michael

doi:10.1016/j.bbagen.2006.08.023

Cited by 29 publications

(21 citation statements)

References 33 publications

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“…In this case the observed anti-coagulant property is due to the depletion of fibrinogen concentration below the threshold level for clotting activity. These serine proteases such as TSV-PA from Trimeresurus stejnegeri venom [8], LV-PA from Agkistrodon halys venom [9] are studied extensively. ''Protac'' from Agkistridon contortrix contortrix venom [10] is the protein C activator and that caused anti-coagulant property.…”

Section: Introductionmentioning

confidence: 99%

Anti-coagulant activity of a metalloprotease: further characterization from the Indian cobra (Naja naja) venom

Kumar

Devaraj

Vishwanath

et al. 2009

J Thromb Thrombolysis

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A high molecular mass, non toxic metalloprotease the NN-PF3 with the bound Ca(2+) and Zn(2+) from the Naja naja venom has been studied further for its anticoagulant property. The molecular mass by MALDI-TOF mass spectrometry was 67.81 kDa. The NN-PF3 exhibited fibrin(ogen)olytic activity. In addition to fibrinogen, NN-PF3 hydrolyzed blood and plasma clot with the later hydrolyzed about one fold higher. The alpha polymer of fibrin was preferentially hydrolyzed over the alpha chain but the beta chain and gamma-gamma dimer remained untouched. It was devoid of plasminogen activation property. It prolonged the activated partial thromboplastin time, prothrombin time and the thrombin clotting time of citrated human plasma. It did not affect the thrombin activity. In mice, defibrinogentaion, prolonged bleeding time (P < 0.01) and reduced fibrinogen level were observed following intravenous injection. Human plasma or alpha2-macroglobulin did not, but the polyvalent anti-venom inhibited the NN-PF3 activity. In contrast to most snake venom metalloproteases, it did not degrade extra cellular matrix proteins.

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Section: Introductionmentioning

confidence: 99%

Anti-coagulant activity of a metalloprotease: further characterization from the Indian cobra (Naja naja) venom

Kumar

Devaraj

Vishwanath

et al. 2009

J Thromb Thrombolysis

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“…It is important to note that the N-terminal region of LV-PA lacks a stretch of positively charged amino acid residues such as the motifs of KHRR found in t-PA and RRHR in u-PA, that have been demonstrated to be involved in the interaction with PAI-1, which is a member of the serine proteinase inhibitors (serpins) superfamily [91,94,95]. Like the other snake venom PAs (TSV-PA and Haly-PA), LV-PA is composed of 234 residues and contains a single N-X-S motif, bearing sugars that account for ~10% of the protein`s total molecular mass of 33 kDa [96].…”

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

confidence: 98%

“…Recent structural studies indicate that the snake venom PAs share a close similarity to t-PA's catalytic domain and to that of nonspecific serine proteinases such as trypsin [95][96][97]. We have examined the effect of the major plasma proteinase inhibitor 2-M towards LV-PA and compared it with the effect on t-PA.…”

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

confidence: 98%

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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“…Zhang et al (1995) firstly isolated T. stejnegeri venom plasminogen activator (TSV-PA), a snake venom protease that specifically activates plasminogen 12) . In addition, other plasminogen activators, namely Haly-PA and LV-PA, have been isolated and purified from the venom of the mainland viper and the jungles of Brazil viper, respectively 13) . Recently, we have successfully isolated and purified the plasminogen activator to homogeneity level from Gloydius brevicaudus venom (GBV-PA) by affinity and reversed-phase chromatography as previously described 14) .…”

Section: Rabbit Ear Vein Thrombosis Studymentioning

confidence: 99%

Thrombolytic and Antiplatelet Effects of a Novel Plasminogen Activator from the Venom of <i>Gloydius Brevicaudus</i> Viper

Zhang

Lin

Zhang³

et al. 2015

JAT

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Aim:To investigate the thrombolytic and antiplatelet effects of a novel plasminogen activator from the venom of Gloydius brevicaudus viper (GBV-PA) in vitro and in vivo. Methods: Thrombolytic experiments were performed in rabbit models of ear vein thrombosis and carotid artery thrombosis and in dog model of acute cerebral infarction. Inhibition of thrombus formation was evaluated in rat inferior vena cava thrombosis model and ferric chloride-induced arterial thrombosis model. In vitro, we assayed the antithrombotic effect of GBV-PA on rabbit blood clots, euglobulin lysis time (ELT) of rabbit plasma, and ADP-induced platelet aggregation. Results: GBV-PA intravenous administration significantly reduced vascular recanalization times of rabbit ear veins thrombosis and thrombus weight of rabbit carotid artery thrombosis. The arterial recanalization rates were dose-and time-dependently improved after the administration of GBV-PA in canine acute cerebral infarction model. Thrombus length and weight were significantly reduced by GBV-PA both in rat inferior vena cava and ferric chloride-induced arterial thrombosis models. Thrombus formation in the blood of rabbits that were administered of GBV-PA was also inhibited. GBV-PA radically reduced plasma ELT of the rabbit's blood clots. ADP-induced platelet aggregation was inhibited by GBV-PA in a dose-dependent manner with a half-maximal inhibitory concentration of 19.9 g/mL. Conclusion: This study demonstrates that GBV-PA is a thrombolytic and antiplatelet agent. It has significant antithrombotic effects on various in vitro and in vivo experimental models of thrombosis. The mechanisms that underline its antithrombotic effects were related to GBV-PA's capabilities of increasing fibrinolytic activity and inhibition of platelet aggregation.

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Biochemical characterization and molecular cloning of a plasminogen activator proteinase (LV-PA) from bushmaster snake venom

Cited by 29 publications

References 33 publications

Anti-coagulant activity of a metalloprotease: further characterization from the Indian cobra (Naja naja) venom

Anti-coagulant activity of a metalloprotease: further characterization from the Indian cobra (Naja naja) venom

Proteases from South American Snake Venoms Affecting Fibrinolysis

Thrombolytic and Antiplatelet Effects of a Novel Plasminogen Activator from the Venom of <i>Gloydius Brevicaudus</i> Viper

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