Cyclic imine toxins from dinoflagellates: a growing family of potent antagonists of the nicotinic acetylcholine receptors.
Cyclic imine toxins from dinoflagellates: a growing family of potent antagonists of the nicotinic acetylcholine receptors.
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DOI：
10.1111/jnc.13995
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发表时间：
2017-08
影响因子：
4.7
通讯作者：
Servent D
中科院分区：
文献类型：
--
作者：
Molgó J;Marchot P;Aráoz R;Benoit E;Iorga BI;Zakarian A;Taylor P;Bourne Y;Servent D
我们介绍了速效、亲脂性大环亚胺毒素的毒理学概况，这是一种与藻华、贝类污染和神经毒性相关的新兴有机化合物家族。在世界范围内，贝类污染事件正在扩大；因此，这些毒素对贝类食品工业的意义值得进一步研究。重点是鞭毛藻物种的生产，它们的化学结构，以及它们与主要天然分子靶点（烟碱乙酰胆碱受体）或可溶乙酰胆碱结合蛋白（用作替代受体模型）相互作用的特定模式。鞭毛藻芥蓝菌（Karenia selliformis）和亚历山大菌（Alexandrium olefeldii / A. peruvianum）参与了裸子二胺和螺内酯的生物合成，而Vulcanodinium rugosum则是pinnatoxins和portimine的生产者。环亚胺毒素的特征是由14至27个碳原子组成的大环骨架，两侧有两个保守的环亚胺和螺旋环系统。这些藻毒素通常对肌肉型和神经元型烟碱乙酰胆碱受体表现出高亲和力和广泛特异性，这一特征与它们在受体亚基界面的结合位点一致，它们由在所有nachr中高度保守的残基组成，并解释了动物物种之间的不同毒性。来自鞭毛藻的速效亲脂性大环亚胺分子形成了一个与藻华、贝类污染和神经毒性相关的新兴毒素家族。这篇综述涵盖了它们的生产、化学结构以及它们与主要天然分子靶点（nachr）或可溶性替代受体（AChBP）相互作用的特定模式。
We present an overview of the toxicological profile of the fast acting, lipophilic macrocyclic imine toxins, an emerging family of organic compounds associated with algal blooms, shellfish contamination and neurotoxicity. Worldwide, shellfish contamination incidents are expanding; therefore the significance of these toxins for the shellfish food industry deserves further study. Emphasis is directed to the dinoflagellate species involved in their production, their chemical structures, and their specific mode of interaction with their principal natural molecular targets, the nicotinic acetylcholine receptors, or with the soluble acetylcholine-binding protein, used as a surrogate receptor model. The dinoflagellates Karenia selliformis and Alexandrium ostenfeldii / A. peruvianum have been implicated in the biosynthesis of gymnodimines and spirolides, while Vulcanodinium rugosum is the producer of pinnatoxins and portimine. The cyclic imine toxins are characterized by a macrocyclic skeleton comprising 14 to 27 carbon atoms, flanked by two conserved moieties, the cyclic imine and the spiroketal ring system. These phycotoxins generally display high affinity and broad specificity for the muscle-type and neuronal nicotinic acetylcholine receptors, a feature consistent with their binding site at the receptor subunit interfaces, composed of residues highly conserved among all nAChRs, and explaining the diverse toxicity among animal species. Fast acting, lipophilic macrocyclic imine molecules from dinoflagellates form an emerging family of toxins associated with algal blooms, shellfish contamination and neurotoxicity. This overview covers the species involved in their production, their chemical structures, and their specific modes of interaction with their principal natural molecular targets, the nAChRs, or with the soluble surrogate receptor model, AChBP.
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影响因子：
15
作者：
Araoz, Romulo;Servent, Denis;Molgo, Jordi;Iorga, Bogdan I.;Fruchart-Gaillard, Carole;Benoit, Evelyne;Gu, Zhenhua;Stivala, Craig;Zakarian, Armen
通讯作者：
Zakarian, Armen
影响因子：
6.6
作者：
Anderson DM;Alpermann TJ;Cembella AD;Collos Y;Masseret E;Montresor M
通讯作者：
Montresor M
影响因子：
7.4
作者：
Araoz, Romulo;Ramos, Suzanne;Molgo, Jordi
通讯作者：
Molgo, Jordi
影响因子：
6.6
作者：
Almandoz, Gaston O.;Montoya, Nora G.;Ferrario, Martha E.
通讯作者：
Ferrario, Martha E.
影响因子：
3.7
作者：
Gu, Haifeng
通讯作者：
Gu, Haifeng