Prothrombin activator-like toxin appears to mediate cardiovascular collapse following envenoming by Pseudonaja textilis

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Abstract

Brown snake (Pseudonaja spp.)-induced early cardiovascular collapse is a life-threatening medical emergency in Australia. We have previously shown that this effect can be mimicked in animals and is mediated via the release of endogenous mediators. In the present study, we aimed to purify and characterize the component in Pseudonaja textilis venom which induces cardiovascular collapse following envenoming. The component (fraction 3) was isolated using a combination of techniques including hydroxyapatite and reverse phase chromatography. Fraction 3 (10 or 20 mug/kg, i.v.) produced a rapid decrease in mean arterial pressure (MAP) followed by cardiovascular collapse. Fraction 3-induced early collapse was abolished by prior administration of smaller priming doses of fraction 3 (i.e. 2 and 5 mug/kg, i.v.) or heparin (300 units/kg, i.v.). P. textilis whole venom (1 and 3 mug/ml), but not fraction 3 (1 or 3 mug/ml), induced endothelium-dependent relaxation in isolated rat mesenteric arteries. SDS-PAGE gel indicated the presence of 9-10 protein bands of fraction 3. Using proteomic based analysis some protein bands of fraction 3 were identified as subunits of venom prothrombin activator, pseutarin C of P. textilis venom. Our results conclude that prothrombin activator-like toxin is likely to be a contributor to the rapid collapse induced by P. textilis venom.
Original languageEnglish
Pages (from-to)48 - 54
Number of pages7
JournalToxicon : official journal of the International Society on Toxinology
Volume102
DOIs
Publication statusPublished - 2015

Cite this

@article{a6e5961f6aff47159ac1451d63bd9cc6,
title = "Prothrombin activator-like toxin appears to mediate cardiovascular collapse following envenoming by Pseudonaja textilis",
abstract = "Brown snake (Pseudonaja spp.)-induced early cardiovascular collapse is a life-threatening medical emergency in Australia. We have previously shown that this effect can be mimicked in animals and is mediated via the release of endogenous mediators. In the present study, we aimed to purify and characterize the component in Pseudonaja textilis venom which induces cardiovascular collapse following envenoming. The component (fraction 3) was isolated using a combination of techniques including hydroxyapatite and reverse phase chromatography. Fraction 3 (10 or 20 mug/kg, i.v.) produced a rapid decrease in mean arterial pressure (MAP) followed by cardiovascular collapse. Fraction 3-induced early collapse was abolished by prior administration of smaller priming doses of fraction 3 (i.e. 2 and 5 mug/kg, i.v.) or heparin (300 units/kg, i.v.). P. textilis whole venom (1 and 3 mug/ml), but not fraction 3 (1 or 3 mug/ml), induced endothelium-dependent relaxation in isolated rat mesenteric arteries. SDS-PAGE gel indicated the presence of 9-10 protein bands of fraction 3. Using proteomic based analysis some protein bands of fraction 3 were identified as subunits of venom prothrombin activator, pseutarin C of P. textilis venom. Our results conclude that prothrombin activator-like toxin is likely to be a contributor to the rapid collapse induced by P. textilis venom.",
author = "Janeyuth Chaisakul and Isbister, {Geoffrey K} and O'Leary, {Margaret A} and Parkington, {Helena C} and Smith, {A Ian} and Hodgson, {Wayne Clarence} and Kuruppu, {D M Sanjaya}",
year = "2015",
doi = "10.1016/j.toxicon.2015.05.001",
language = "English",
volume = "102",
pages = "48 -- 54",
journal = "Toxicon : official journal of the International Society on Toxinology",
issn = "0041-0101",
publisher = "Elsevier",

}

TY - JOUR

T1 - Prothrombin activator-like toxin appears to mediate cardiovascular collapse following envenoming by Pseudonaja textilis

AU - Chaisakul, Janeyuth

AU - Isbister, Geoffrey K

AU - O'Leary, Margaret A

AU - Parkington, Helena C

AU - Smith, A Ian

AU - Hodgson, Wayne Clarence

AU - Kuruppu, D M Sanjaya

PY - 2015

Y1 - 2015

N2 - Brown snake (Pseudonaja spp.)-induced early cardiovascular collapse is a life-threatening medical emergency in Australia. We have previously shown that this effect can be mimicked in animals and is mediated via the release of endogenous mediators. In the present study, we aimed to purify and characterize the component in Pseudonaja textilis venom which induces cardiovascular collapse following envenoming. The component (fraction 3) was isolated using a combination of techniques including hydroxyapatite and reverse phase chromatography. Fraction 3 (10 or 20 mug/kg, i.v.) produced a rapid decrease in mean arterial pressure (MAP) followed by cardiovascular collapse. Fraction 3-induced early collapse was abolished by prior administration of smaller priming doses of fraction 3 (i.e. 2 and 5 mug/kg, i.v.) or heparin (300 units/kg, i.v.). P. textilis whole venom (1 and 3 mug/ml), but not fraction 3 (1 or 3 mug/ml), induced endothelium-dependent relaxation in isolated rat mesenteric arteries. SDS-PAGE gel indicated the presence of 9-10 protein bands of fraction 3. Using proteomic based analysis some protein bands of fraction 3 were identified as subunits of venom prothrombin activator, pseutarin C of P. textilis venom. Our results conclude that prothrombin activator-like toxin is likely to be a contributor to the rapid collapse induced by P. textilis venom.

AB - Brown snake (Pseudonaja spp.)-induced early cardiovascular collapse is a life-threatening medical emergency in Australia. We have previously shown that this effect can be mimicked in animals and is mediated via the release of endogenous mediators. In the present study, we aimed to purify and characterize the component in Pseudonaja textilis venom which induces cardiovascular collapse following envenoming. The component (fraction 3) was isolated using a combination of techniques including hydroxyapatite and reverse phase chromatography. Fraction 3 (10 or 20 mug/kg, i.v.) produced a rapid decrease in mean arterial pressure (MAP) followed by cardiovascular collapse. Fraction 3-induced early collapse was abolished by prior administration of smaller priming doses of fraction 3 (i.e. 2 and 5 mug/kg, i.v.) or heparin (300 units/kg, i.v.). P. textilis whole venom (1 and 3 mug/ml), but not fraction 3 (1 or 3 mug/ml), induced endothelium-dependent relaxation in isolated rat mesenteric arteries. SDS-PAGE gel indicated the presence of 9-10 protein bands of fraction 3. Using proteomic based analysis some protein bands of fraction 3 were identified as subunits of venom prothrombin activator, pseutarin C of P. textilis venom. Our results conclude that prothrombin activator-like toxin is likely to be a contributor to the rapid collapse induced by P. textilis venom.

UR - http://www.sciencedirect.com/science/article/pii/S0041010115001245

U2 - 10.1016/j.toxicon.2015.05.001

DO - 10.1016/j.toxicon.2015.05.001

M3 - Article

VL - 102

SP - 48

EP - 54

JO - Toxicon : official journal of the International Society on Toxinology

JF - Toxicon : official journal of the International Society on Toxinology

SN - 0041-0101

ER -