Mechanisms Responsible for the Anticoagulant Properties of Neurotoxic Dendroaspis Venoms: A Viscoelastic Analysis
AffiliationUniv Arizona, Coll Med, Dept Anesthesiol
MetadataShow full item record
CitationNielsen, V. G., Wagner, M. T., & Frank, N. (2020). Mechanisms Responsible for the Anticoagulant Properties of Neurotoxic Dendroaspis Venoms: A Viscoelastic Analysis. International journal of molecular sciences, 21(6), 2082.
Rights© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractUsing thrombelastography to gain mechanistic insights, recent investigations have identified enzymes and compounds in Naja and Crotalus species' neurotoxic venoms that are anticoagulant in nature. The neurotoxic venoms of the four extant species of Dendroaspis (the Black and green mambas) were noted to be anticoagulant in nature in human blood, but the mechanisms underlying these observations have never been explored. The venom proteomes of these venoms are unique, primarily composed of three finger toxins (3-FTx), Kunitz-type serine protease inhibitors (Kunitz-type SPI) and <7% metalloproteinases. The anticoagulant potency of the four mamba venoms available were determined in human plasma via thrombelastography; vulnerability to inhibition of anticoagulant activity to ethylenediaminetetraacetic acid (EDTA) was assessed, and inhibition of anticoagulant activity after exposure to a ruthenium (Ru)-based carbon monoxide releasing molecule (CORM-2) was quantified. Black mamba venom was the least potent by more than two orders of magnitude compared to the green mamba venoms tested; further, Black Mamba venom anticoagulant activity was not inhibited by either EDTA or CORM-2. In contrast, the anticoagulant activities of the green mamba venoms were all inhibited by EDTA to a greater or lesser extent, and all had anticoagulation inhibited with CORM-2. Critically, CORM-2-mediated inhibition was independent of carbon monoxide release, but was dependent on a putative Ru-based species formed from CORM-2. In conclusion, there was great species-specific variation in potency and mechanism(s) responsible for the anticoagulant activity of Dendroaspis venom, with perhaps all three protein classes-3-FTx, Kunitz-type SPI and metalloproteinases-playing a role in the venoms characterized.
NoteOpen access journal
VersionFinal published version
Except where otherwise noted, this item's license is described as © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
- The medical threat of mamba envenoming in sub-Saharan Africa revealed by genus-wide analysis of venom composition, toxicity and antivenomics profiling of available antivenoms.
- Authors: Ainsworth S, Petras D, Engmark M, Süssmuth RD, Whiteley G, Albulescu LO, Kazandjian TD, Wagstaff SC, Rowley P, Wüster W, Dorrestein PC, Arias AS, Gutiérrez JM, Harrison RA, Casewell NR, Calvete JJ
- Issue date: 2018 Feb 10
- Top-down venomics of the East African green mamba, Dendroaspis angusticeps, and the black mamba, Dendroaspis polylepis, highlight the complexity of their toxin arsenals.
- Authors: Petras D, Heiss P, Harrison RA, Süssmuth RD, Calvete JJ
- Issue date: 2016 Sep 2
- Toxicovenomics and antivenom profiling of the Eastern green mamba snake (Dendroaspis angusticeps).
- Authors: Lauridsen LP, Laustsen AH, Lomonte B, Gutiérrez JM
- Issue date: 2016 Mar 16
- Anticoagulant activity of krait, coral snake, and cobra neurotoxic venoms with diverse proteomes are inhibited by carbon monoxide.
- Authors: Nielsen VG, Frank N, Turchioe BJ
- Issue date: 2019 Dec
- Unveiling the nature of black mamba (Dendroaspis polylepis) venom through venomics and antivenom immunoprofiling: Identification of key toxin targets for antivenom development.
- Authors: Laustsen AH, Lomonte B, Lohse B, Fernández J, Gutiérrez JM
- Issue date: 2015 Apr 24