State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Macau, China.
Pilot Laboratory and Proteomics Core, Faculty of Health Sciences, University of Macau, Macau, China.
Arch Toxicol. 2019 Jun;93(6):1745-1767. doi: 10.1007/s00204-019-02456-z. Epub 2019 Jun 15.
Venoms from marine animals have been recognized as a new emerging source of peptide-based therapeutics. Several peptide toxins from sea anemone have been investigated as therapeutic leads or pharmacological tools. Venom complexity should be further highlighted using combined strategies of large-scale sequencing and data analysis which integrated transcriptomics and proteomics to elucidate new proteins or peptides to be compared among species. In this work, transcriptomic and proteomic analyses were combined to identify six groups of expressed peptide toxins in Zoanthus natalensis. These include neurotoxin, hemostatic and hemorrhagic toxin, protease inhibitor, mixed function enzymes, venom auxiliary proteins, allergen peptides, and peptides related to the innate immunity. Molecular docking analysis indicated that one expressed Zoanthus Kunitz-like peptide, ZoaKuz1, could be a voltage-gated potassium channels blocker and, hence, it was selected for functional studies. Functional bioassays revealed that ZoaKuz1 has an intrinsic neuroprotective activity in zebrafish model of Parkinson's disease. Since pharmacological blockade of K channels is known to induce neuroprotective effects, ZoaKuz1 holds the potential to be developed in a therapeutic tool to control neural dysfunction by slowing or even halting neurodegeneration mediated by ion-channel hyperactivity.
海洋动物毒液已被视为基于肽的治疗药物的新来源。已经研究了几种来自海葵的肽毒素,将其作为治疗先导物或药理学工具。应使用大规模测序和数据分析的联合策略进一步突出毒液的复杂性,该策略整合了转录组学和蛋白质组学,以阐明新的蛋白质或肽,以便在物种之间进行比较。在这项工作中,结合了转录组学和蛋白质组学分析,以鉴定纳塔尔氏海葵中的 6 组表达的肽毒素。这些包括神经毒素、止血和出血毒素、蛋白酶抑制剂、混合功能酶、毒液辅助蛋白、过敏原肽和与先天免疫相关的肽。分子对接分析表明,一种表达的海葵 Kunitz 样肽 ZoaKuz1 可以作为电压门控钾通道阻断剂,因此选择其进行功能研究。功能生物测定显示,ZoaKuz1 在帕金森病的斑马鱼模型中具有内在的神经保护活性。由于已知钾通道的药理学阻断会引起神经保护作用,因此 ZoaKuz1 有可能被开发为治疗工具,通过减缓甚至阻止由离子通道过度活跃介导的神经退行性变来控制神经功能障碍。