Butzke Daniel, Luch Andreas
Center for Alternatives to Animal Experiments (ZEBET), Federal Institute for Risk Assessment, Berlin, Germany.
EXS. 2010;100:213-32. doi: 10.1007/978-3-7643-8338-1_6.
High-molecular weight protein toxins significantly contribute to envenomations by certain marine invertebrates, e.g., jellyfish and fire corals. Toxic proteins frequently evolved from enzymes meant to be employed primarily for digestive purposes. The cellular intermediates produced by such enzymatic activity, e.g., reactive oxygen species or lysophospholipids, rapidly and effectively mediate cell death by disrupting cellular integrity. Membrane integrity may also be disrupted by pore-forming toxins that do not exert inherent enzymatic activity. When targeted to specific pharmacologically relevant sites in tissues or cells of the natural enemy or prey, toxic enzymes or pore-forming toxins even may provoke fast and severe systemic reactions. Since toxin-encoding genes constitute "hot spots" of molecular evolution, continuous variation and acquirement of new pharmacological properties are guaranteed. This also makes individual properties and specificities of complex proteinaceous venoms highly diverse and inconstant. In the present chapter we portray high-molecular weight constituents of venoms present in box jellyfish, sea anemones, sea hares, fire corals and the crown-of-thorns starfish. The focus lies on the latest achievements in the attempt to elucidate their molecular modes of action.
高分子量蛋白质毒素在某些海洋无脊椎动物(如水母和火珊瑚)的毒液中起着重要作用。有毒蛋白质通常由主要用于消化目的的酶进化而来。这种酶促活性产生的细胞中间体,如活性氧或溶血磷脂,通过破坏细胞完整性迅速而有效地介导细胞死亡。不具有固有酶活性的成孔毒素也可能破坏膜的完整性。当靶向天敌或猎物组织或细胞中的特定药理学相关位点时,有毒酶或成孔毒素甚至可能引发快速而严重的全身反应。由于毒素编码基因构成了分子进化的“热点”,因此可以保证其不断变异并获得新的药理学特性。这也使得复杂蛋白质毒液的个体特性和特异性高度多样且不稳定。在本章中,我们描述了箱形水母、海葵、海兔、火珊瑚和棘冠海星毒液中的高分子量成分。重点在于阐明其分子作用模式的最新研究成果。