Neale Vanessa, Smout Michael J, Seymour Jamie E
College of Public Health, Medical and Veterinary Sciences, James Cook University, McGregor Road, Smithfield, Cairns 4878, Australia; Australian Institute of Tropical Health and Medicine (AITHM) and Centre for Biodiscovery and Molecular Development of Therapeutics (CBMDT), James Cook University, McGregor Road, Smithfield, Cairns 4878, Australia.
Australian Institute of Tropical Health and Medicine (AITHM) and Centre for Biodiscovery and Molecular Development of Therapeutics (CBMDT), James Cook University, McGregor Road, Smithfield, Cairns 4878, Australia.
Toxicon. 2018 Mar 1;143:108-117. doi: 10.1016/j.toxicon.2018.01.009. Epub 2018 Jan 31.
For the first time the impedance-based xCELLigence real-time cell analysis system was used to measure the myotoxicity of sea snake venom. With a focus on the spine-bellied sea snake (Hydrophis curtus), the venom of four sea snake species and three terrestrial snake species were compared for myotoxicity against a human skeletal muscle cell line (HSkMC). Hydrophis curtus venom was also tested on a human cardiac muscle cell line (HCM). Surprisingly, all four sea snake venoms tested on HSkMC produced an initial 100-280% rise in xCELLigence cell index that peaked within the first two hours before falling. The cell index rise of H. curtus venom was correlated with the WST-1 cell proliferation assay, which demonstrated an increase in mitochondrial metabolism. The myotoxicity of H. curtus was 4.7-8.2 fold less potent than the other sea snakes tested, the Australian beaked sea snake (Hydrophis zweifeli), the elegant sea snake (Hydrophis elegans) and the olive sea snake (Aipysurus laevis). If our cell-based results translate to H. curtus envenomations, this implies that H. curtus would be less myotoxic than the other three. Yet the myotoxicity of H. curtus venom to cardiac muscle cells was nine times weaker than for skeletal muscle cells, providing evidence that the venom has a selective effect on skeletal muscle cells. This evidence, combined with the slow-acting nature of the venom, supports a digestive role for sea snake myotoxins.
首次使用基于阻抗的xCELLigence实时细胞分析系统来测量海蛇毒液的肌毒性。以棘腹海蛇（Hydrophis curtus）为重点，比较了四种海蛇和三种陆蛇的毒液对人骨骼肌细胞系（HSkMC）的肌毒性。还在人心肌细胞系（HCM）上测试了棘腹海蛇毒液。令人惊讶的是，在HSkMC上测试的所有四种海蛇毒液都使xCELLigence细胞指数最初上升了100%-280%，在最初两小时内达到峰值，然后下降。棘腹海蛇毒液的细胞指数上升与WST-1细胞增殖试验相关，该试验表明线粒体代谢增加。棘腹海蛇的肌毒性比其他测试的海蛇，即澳大利亚喙海蛇（Hydrophis zweifeli）、秀丽海蛇（Hydrophis elegans）和橄榄海蛇（Aipysurus laevis）低4.7-8.2倍。如果我们基于细胞的结果适用于棘腹海蛇咬伤，这意味着棘腹海蛇的肌毒性比其他三种海蛇小。然而，棘腹海蛇毒液对心肌细胞的肌毒性比对骨骼肌细胞弱九倍，这证明毒液对骨骼肌细胞有选择性作用。这一证据，再加上毒液作用缓慢的特性，支持了海蛇肌毒素具有消化作用的观点。
