Protein C activation by an activator purified from the venom of Agkistrodon halys halys

Bakker, Harry M.; Tans, Guido; Yukel'son, L. Ya.; Janssen-Claessen, Truus; Bertina, R. M.; Hemker, H.C.; Rosing, Jan

doi:10.1097/00001721-199308000-00012

Cited by 14 publications

(11 citation statements)

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“…It also stimulates fi brinolysis through its interaction with plasminogen activator inhibitor [44][45][46] . A number of snake venoms specifi cally activate protein C [47] [47][48][49][50][51][52] , A. bilineatus [53] , A. h. halys [54] , and A. blomhoffi ussuriensis [55] . They are glycoproteins with a molecular mass of ϳ 36-40 kDa.…”

Section: Protein C Activatorsmentioning

confidence: 99%

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Serine Proteases Affecting Blood Coagulation and Fibrinolysis from Snake Venoms

Kini

2005

Pathophysiol Haemos Thromb

160

106

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Snake venom proteases, in addition to their contribution to the digestion of the prey, affect various physiological functions. They affect platelet aggregation, blood coagulation, fibrinolysis, complement system, blood pressure and nervous system. This review provides a ready reference for serine proteases that interfere in blood coagulation and fibrinolysis. They exhibit their activity by activation of specific zymogens of coagulation factors. These serine proteases serve as tools to study molecular details in the activation of specific factors involved in coagulation and fibrinolytic cascades and are useful in treating various thrombotic and hemostatic conditions.

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Section: Protein C Activatorsmentioning

confidence: 99%

“…These serine proteases activate protein C at low salt concentration in the absence of Ca 2+ ions. High salt and Ca 2+ ions inhibit their ability to activate protein C [49,51,54] . So far, amino acid sequence of only the protein C activator from A. c. contortrix venom has been determined [56] .…”

Section: Protein C Activatorsmentioning

confidence: 99%

Serine Proteases Affecting Blood Coagulation and Fibrinolysis from Snake Venoms

Kini

2005

Pathophysiol Haemos Thromb

160

106

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“…The following snake venoms have been described to contain PC activators [12][13][14][15][16][17] First results on the isolation of thrombomodulin-independent and fast-activating PC activator from A. contortrix contortrix (southern copperhead snake), and related PC-activating properties of enzymes from venom of Agkistrodon subspecies and in venom of A. piscivorus (eastern cottonmouth snake), Agkistrodon bilineatus (tropical moccasin snake), B. moojeni, B. pradoi (Prado's pit viper), Vipera lebetina (desert adder) and Cerastes cerastes (Egyptian sand viper) were presented in 1985 at the Symposium on Animal Venoms and Hemostasis in San Diego, Calif. [18].…”

Section: Pc Activatorsmentioning

confidence: 99%

“…A PC activator with a molecular weight of 36,000-40,000 D and an antithrombotic effect in rats [14,32] has been isolated from A. halys halys (Asian pit viper) venom. The difference between PC activators from New and Old World snake venom consists in the fact that PC activators from Agkistrodon from the New World have a molecular weight of less than 40,000 D and a pH optimum of 7.0-8.5, and activate PC from rat plasma to a lesser extent than PC from human plasma.…”

Section: Protein C Activators From Old World Species Of the Genus Agkmentioning

confidence: 99%

Protein C Activators from Snake Venoms and Their Diagnostic Use

Gempeler-Messina¹,

Volz²,

Bühler³

et al. 2001

Pathophysiol Haemos Thromb

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Proteinases converting the zymogen protein C (PC) of vertebrates into activated PC have been detected in several snake venoms. Most PC activators have been purified from venom of snake species belonging to the genera of the Agkistrodon complex. Unlike the physiological, thrombin-catalyzed PC activation reaction which requires thrombomodulin as a cofactor, most snake venom activators directly convert the zymogen PC into the catalytically active form which can easily be determined by means of coagulation or chromogenic substrate techniques. Due to this feature, the fast-acting PC activator Protac^®from Agkistrodon contortrix contortrix (southern copperhead snake) venom has found a broad application in diagnostic practice for the determination of disorders in the PC pathway. Recently, screening assays for the PC pathway have been introduced, based on the observation that the PC pathway is probably the most important physiological barrier against thrombosis.

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“…Procoagulation and the varying effects of anticoagulation are the major focal points of this thesis. Procoagulant toxins can be simplified into four groups: prothrombin activators (Bos and Camire, 2010;Joseph and Kini, 2002;Kini, 2005a;Kornalik and Blombäck, 1975;Pirkle et al, 1972;Rogalski et al, 2017;Rosing and Tans, 1992;Yamada et al, 1996), Factor X activators (Chen et al, 2008;Joseph and Kini, 2002;Oulion et al, 2018;Tans and Rosing, 2002;Yamada et al, 1997), Factor V activators (Bos and Camire, 2010;Bos et al, 2016;Rosing et al, 2001;Williams et al, 1994;Zdenek et al, 2019), and thrombin-like enzymes (Cho et al, 2001;Esnouf and Tunnah, 1967;Huang et al, 2011;Lin et al, 2009;Nielsen, 2016b;Teng, 1976, 1978;Pradniwat and Rojnuckarin, 2015;Tan, 2010;Tan et al, 2012;Zhang et al, 2007), while anticoagulants can affect any number of factors singularly or synergistically, such as blocking clotting enzymes while activating Protein C (Bakker et al, 1993;Esmon et al, 1987;Jin and Gopinath, 2016;Kisiel et al, 1987;Kogan et al, 1993;Nakagaki et al, 1990). These types of activators or inhibitors have been found and isolated from a number of varying families and species of venomous snakes.…”

Section: Snake Venoms and Coagulationmentioning

confidence: 99%

A blood bond: evolutionary, pathophysiological and biodiscovery implications of coagulotoxic snake venoms

Debono¹

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Snakebite is a massive global burden and is a neglected area of tropical diseases. Snake venom neurotoxins have been the subject of intense research efforts, albeit significantly less is known about coagulotoxins. Venoms can deleteriously affect any physiological system reachable by the bloodstream, including being able to directly interfere with the coagulation cascade. Such coagulopathic toxins may be either anticoagulant or procoagulant and snake venoms are unique in their use of procoagulant toxins for predatory purposes. Our limited knowledge into the mechanisms of action of snake venom hinders our understanding of the clinical pathologies and also restricts our use of these powerful natural products as lead compounds in drug design and development. Two snake families which exhibit coagulant properties and lead to a range of clinical pathologies are vipers, Viperidae, and non-front-fanged snakes, Colubridae. The primary focus of this thesis was to investigate and compare the coagulotoxicity effects and mechanisms of various species of known venomous snakes that effect coagulation. Species chosen for this investigation have had limited previous research conducted, thus a knowledge gap in the literature remains. These coagulant properties were investigated through a multi-disciplinary approach, highlighting key results from both families.Data chapters 2 and 3 explore venom from the boomslang (Dispholidus typus) and the twig snakes (Thelotornis species) -iconic African snakes belonging to the family Colubridae. Both species produce strikingly similar lethal procoagulant pathologies. Despite these similarities, antivenom is only produced for treating bites by D. typus, and the mechanisms of action of both venoms have been understudied. We found that T. mossambicanus produced a significantly stronger coagulation response compared to D. typus, governed by strong prothrombin activation through PIII-SVMPs.Despite similarities in symptoms and clinical manifestations, venom composition differs widely between the two species, recovered from a combined approach of venomics and transcriptomics. The neutralising capability of the available boomslang antivenom was also investigated on both species, with it being 11.3 times more effective upon D. typus venom than T. mossambicanus. Envenomation by Crotalinae such as Asian pit vipers can induce multiple clinical complications resulting from coagulopathic and neuropathic effects. Data chapters 4 -8 investigate the Asian Pit Viper clade. While intense research has been undertaken for some species, such as Calloselasma rhodostoma, functional coagulopathic effects have been neglected. As these species' venoms affect the blood coagulation cascade and are known to produce haemorrhagic shock in envenomed patients, we investigated their effects upon coagulation using venoms of 33 species from the Asian pit viper clade including Azemiops, Calloselasma, Deinagkistrodon, Gloydius, Hypnale, Protobothrops, Trimeresurus and Tropidolaemus. Fibrinogen was the main coagulation target among th...

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Protein C activation by an activator purified from the venom of Agkistrodon halys halys

Cited by 14 publications

References 0 publications

Serine Proteases Affecting Blood Coagulation and Fibrinolysis from Snake Venoms

Serine Proteases Affecting Blood Coagulation and Fibrinolysis from Snake Venoms

Protein C Activators from Snake Venoms and Their Diagnostic Use

A blood bond: evolutionary, pathophysiological and biodiscovery implications of coagulotoxic snake venoms

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