Elucidation of Medusozoan (Jellyfish) Venom Constituent Activities Using Constellation Pharmacology.

IF 3.9 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Toxins Pub Date : 2024-10-17 DOI:10.3390/toxins16100447
Angel A Yanagihara, Matías L Giglio, Kikiana Hurwitz, Raechel Kadler, Samuel S Espino, Shrinivasan Raghuraman, Baldomero M Olivera
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Abstract

Within the phylum Cnidaria, sea anemones (class Anthozoa) express a rich diversity of ion-channel peptide modulators with biomedical applications, but corollary discoveries from jellyfish (subphylum Medusozoa) are lacking. To bridge this gap, bioactivities of previously unexplored proteinaceous and small molecular weight (~15 kDa to 5 kDa) venom components were assessed in a mouse dorsal root ganglia (DRG) high-content calcium-imaging assay, known as constellation pharmacology. While the addition of crude venom led to nonspecific cell death and Fura-2 signal leakage due to pore-forming activity, purified small molecular weight fractions of venom demonstrated three main, concentration-dependent and reversible effects on defined heterogeneous cell types found in the primary cultures of mouse DRG. These three phenotypic responses are herein referred to as phenotype A, B and C: excitatory amplification (A) or inhibition (B) of KCl-induced calcium signals, and test compound-induced disturbances to baseline calcium levels (C). Most notably, certain Alatina alata venom fractions showed phenotype A effects in all DRG neurons; Physalia physalis and Chironex fleckeri fractions predominantly showed phenotype B effects in small- and medium-diameter neurons. Finally, specific Physalia physalis and Alatina alata venom components induced direct excitatory responses (phenotype C) in glial cells. These findings demonstrate a diversity of neuroactive compounds in jellyfish venom potentially targeting a constellation of ion channels and ligand-gated receptors with broad physiological implications.

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利用星座药理学阐明介壳虫(水母)毒液成分的活性。
在刺胞动物门中,海葵(Anthozoa 类)表达了丰富多样的具有生物医学应用价值的离子通道肽调节剂,但水母(Medusozoa 亚门)却缺乏相应的发现。为了弥补这一差距,我们在小鼠背根神经节(DRG)高浓度钙成像试验(即星座药理学)中评估了以前未探索过的蛋白质和小分子量(约 15 kDa 至 5 kDa)毒液成分的生物活性。加入粗制毒液会导致非特异性细胞死亡,并因孔隙形成活性而导致 Fura-2 信号泄漏,而纯化的小分子量毒液组分则对小鼠背根神经节原代培养物中定义的异质细胞类型产生了三种主要的、浓度依赖性的可逆效应。这三种表型反应在此称为表型 A、B 和 C:KCl 诱导的钙信号的兴奋性放大(A)或抑制(B),以及测试化合物诱发的基线钙水平紊乱(C)。最值得注意的是,某些 Alatina alata 毒液组分在所有 DRG 神经元中都表现出表型 A 效应;而 Physalia physalis 和 Chironex fleckeri组分则主要在中小直径神经元中表现出表型 B 效应。最后,特定的 Physalia physalis 和 Alatina alata 毒液成分可诱导神经胶质细胞产生直接兴奋反应(表型 C)。这些研究结果表明,水母毒液中的神经活性化合物种类繁多,可能针对一系列具有广泛生理影响的离子通道和配体门控受体。
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来源期刊
Toxins
Toxins TOXICOLOGY-
CiteScore
7.50
自引率
16.70%
发文量
765
审稿时长
16.24 days
期刊介绍: Toxins (ISSN 2072-6651) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to toxins and toxinology. It publishes reviews, regular research papers and short communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced.
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