Nature of Peptides Released by Thrombin

Gladner, Jules A.; Murtaugh, Patricia A.; Folk, J.E.; Laki, K.

doi:10.1111/j.1749-6632.1963.tb17651.x

Cited by 50 publications

(3 citation statements)

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“…At first glance, it might appear contradictory for snakes to employ both procoagulant and anticoagulant enzymes, but in reality, this is a well-coordinated strategy to render the prey’s blood wholly incoagulable with astonishing speed. Venom thrombin-like enzymes (TLEs) consume fibrinogen, yielding small fibrin clots, and hypotensive fibrinopeptides [ 77 , 78 ]. However, the commencement of inappropriate clotting triggers the prey’s anti-clotting cascade, which rapidly destroys the fibrin clots [ 79 ].…”

Section: Resultsmentioning

confidence: 99%

Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly

et al. 2015

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BackgroundWhile many studies have shown that extracellular proteins evolve rapidly, how selection acts on them remains poorly understood. We used snake venoms to understand the interaction between ecology, expression level, and evolutionary rate in secreted protein systems. Venomous snakes employ well-integrated systems of proteins and organic constituents to immobilize prey. Venoms are generally optimized to subdue preferred prey more effectively than non-prey, and many venom protein families manifest positive selection and rapid gene family diversification. Although previous studies have illuminated how individual venom protein families evolve, how selection acts on venoms as integrated systems, is unknown.ResultsUsing next-generation transcriptome sequencing and mass spectrometry, we examined microevolution in two pitvipers, allopatrically separated for at least 1.6 million years, and their hybrids. Transcriptomes of parental species had generally similar compositions in regard to protein families, but for a given protein family, the homologs present and concentrations thereof sometimes differed dramatically. For instance, a phospholipase A2 transcript comprising 73.4 % of the Protobothrops elegans transcriptome, was barely present in the P. flavoviridis transcriptome (<0.05 %). Hybrids produced most proteins found in both parental venoms. Protein evolutionary rates were positively correlated with transcriptomic and proteomic abundances, and the most abundant proteins showed positive selection. This pattern holds with the addition of four other published crotaline transcriptomes, from two more genera, and also for the recently published king cobra genome, suggesting that rapid evolution of abundant proteins may be generally true for snake venoms. Looking more broadly at Protobothrops, we show that rapid evolution of the most abundant components is due to positive selection, suggesting an interplay between abundance and adaptation.ConclusionsGiven log-scale differences in toxin abundance, which are likely correlated with biosynthetic costs, we hypothesize that as a result of natural selection, snakes optimize return on energetic investment by producing more of venom proteins that increase their fitness. Natural selection then acts on the additive genetic variance of these components, in proportion to their contributions to overall fitness. Adaptive evolution of venoms may occur most rapidly through changes in expression levels that alter fitness contributions, and thus the strength of selection acting on specific secretome components.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1832-6) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly

et al. 2015

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“…The ability to stimulate frog heart by the extracted clot liquors obtained after conversion of Fg to fibrin by thrombin was first mentioned in 1951 (Laki 1951). It was then found that fibrinopeptide-B, which is obtained as a result of Fg conversion to fibrin by thrombin, can increase bradykinin-induced contraction of isolated rat uterus in the oestrus cycle (Gladner et al 1963). Further studies have shown short-lasting effects of fibrinopeptides A and B on arterial blood pressure in rats (Barczak-Osinska et al 1983).…”

Section: Fg and Vasoactivitymentioning

confidence: 99%

Mechanisms of fibrinogen‐induced microvascular dysfunction during cardiovascular disease

et al. 2009

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Fibrinogen (Fg) is a high molecular weight plasma adhesion protein and a biomarker of inflammation. Many cardiovascular and cerebrovascular disorders are accompanied by increased blood content of Fg. Increased levels of Fg result in changes in blood rheological properties such as increases in plasma viscosity, erythrocyte aggregation, platelet thrombogenesis, alterations in vascular reactivity and compromises in endothelial layer integrity. These alterations exacerbate the complications in peripheral blood circulation during cardiovascular diseases such as hypertension, diabetes and stroke. In addition to affecting blood viscosity by altering plasma viscosity and erythrocyte aggregation, growing experimental evidence suggests that Fg alters vascular reactivity and impairs endothelial cell layer integrity by binding to its endothelial cell membrane receptors and activating signalling mechanisms. The purpose of this review is to discuss experimental data, which demonstrate the effects of Fg causing vascular dysfunction and to offer possible mechanisms for these effects, which could exacerbate microcirculatory complications during cardiovascular diseases accompanied by increased Fg content.

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“…I have been studying the role of fibrinogen/ fibrin degradation products (FDP) in the processes of the organism apart from haemost a s k It is known from the investigations of Gladner et at. (1963) that fibrinopeptides A and B are the results of the reaction of fibrinogen and thrombin and potentiate the contractile effect of bradykinin on the isolated cornu of the rat uterus.…”

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confidence: 99%

40. The Biological and Pharmacological Properties of Some Fibrinogen Degradation Products*

Malofiejew

1971

Scandinavian Journal of Haematology

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Nature of Peptides Released by Thrombin

Cited by 50 publications

References 9 publications

Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly

Snake venoms are integrated systems, but abundant venom proteins evolve more rapidly

Mechanisms of fibrinogen‐induced microvascular dysfunction during cardiovascular disease

40. The Biological and Pharmacological Properties of Some Fibrinogen Degradation Products*

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