Chaisakul Janeyuth, Isbister Geoffrey K, O'Leary Margaret A, Parkington Helena C, Smith A Ian, Hodgson Wayne C, Kuruppu Sanjaya
Monash Venom Group, Department of Pharmacology, Monash University, VIC, 3800, Australia; Department of Pharmacology, Phramongkutklao College of Medicine, Bangkok, 10400, Thailand.
Monash Venom Group, Department of Pharmacology, Monash University, VIC, 3800, Australia; Department of Clinical Pharmacology and Toxicology, Calvary Mater, NSW, 2298, Australia.
Toxicon. 2015 Aug;102:48-54. doi: 10.1016/j.toxicon.2015.05.001. Epub 2015 May 7.
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 μg/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 μg/kg, i.v.) or heparin (300 units/kg, i.v.). P. textilis whole venom (1 and 3 μg/ml), but not fraction 3 (1 or 3 μg/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.
在澳大利亚，棕蛇（伪眼镜蛇属）引起的早期心血管衰竭是一种危及生命的医疗急症。我们之前已经表明，这种效应可以在动物身上模拟出来，并且是通过内源性介质的释放介导的。在本研究中，我们旨在纯化并鉴定细鳞太攀蛇毒液中导致中毒后心血管衰竭的成分。该成分（组分3）通过包括羟基磷灰石和反相色谱在内的多种技术组合进行分离。组分3（10或20μg/kg，静脉注射）可使平均动脉压（MAP）迅速下降，随后出现心血管衰竭。预先给予较小剂量的组分3（即2和5μg/kg，静脉注射）或肝素（300单位/kg，静脉注射）可消除组分3引起的早期衰竭。细鳞太攀蛇全毒液（1和3μg/ml）可诱导离体大鼠肠系膜动脉内皮依赖性舒张，但组分3（1或3μg/ml）则不能。SDS-PAGE凝胶显示组分3存在9-10条蛋白带。通过基于蛋白质组学的分析，组分3的一些蛋白带被鉴定为毒液凝血酶原激活剂的亚基，即细鳞太攀蛇毒液的pseutarin C。我们的结果表明，凝血酶原激活剂样毒素可能是细鳞太攀蛇毒液诱导快速衰竭的一个因素。
