Super-high procoagulant activity of gecko thrombin: A gift from sky dragon.

Gecko, the "sky dragon" named by Traditional Chinese Medicine, undergoes rapid coagulation and scarless regeneration following tail amputation in the natural ecology, providing a perfect opportunity to develop the efficient and safe drug for blood clotting. Here, gecko thrombin (gthrombin) was recombinantly prepared and comparatively studied on its procoagulant activity. The 3D structure of gthrombin was constructed using the homology modeling method of I-TASSER. The active gthrombin was prepared by the expression of gecko prethrombin-2 in 293 T cells, followed by purification with Ni2+ -chelating column chromatography prior to activation by snake venom-derived Ecarin. The enzymatic activities of gthrombin were assayed by hydrolysis of synthetic substrate S-2238 and the fibrinogen clotting. The vulnerable nerve cells were used to evaluate the toxicity of gthrombin at molecular and cellular levels. The active recombinant gthrombin showed super-high catalytic and fibrinogenolytic efficiency than those of human under different temperatures and pH conditions. In addition, gthrombin made nontoxic effects on the central nerve cells including neurons, contrary to those of mammalian counterparts, which contribute to neuronal damage, astrogliosis, and demyelination. A super-high activity but safe procoagulant candidate drug was identified from reptiles, which provided a promising perspective for clinical application in rapid blood clotting. © 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.

Citation

Hao Liang, Xingyuan Zhang, Yuxuan Hou, Kang Zheng, Huifei Hao, Bingqiang He, Hui Li, Chunshuai Sun, Ting Yang, Honghua Song, Rixin Cai, Yingjie Wang, Haiyan Jiang, Lei Qi, Yongjun Wang. Super-high procoagulant activity of gecko thrombin: A gift from sky dragon. CNS neuroscience & therapeutics. 2023 Oct;29(10):3081-3093

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PMID: 37144588

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