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Special Issue "Sea Anemone Toxins"

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A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (31 May 2012)

Special Issue Editor

Guest Editor
Prof. Dr. Hiroshi Nagai

Department of Ocean Science, Tokyo University of Marine Science and Technology, 4-5-7 Konan, Minato-ku, Tokyo 108-8477, Japan

Special Issue Information

Dear Colleagues,

The sea anemones belong to the phylum Cnidaria. The distinguishing feature of cnidarians is nematocysts, specialized venomous organs that the animals use mainly for capturing prey and protecting themselves from predators. This means all the cnidarians have venom. So far, a number of polypeptide toxins have been isolated and characterized from the sea anemones. Among these studies, ion-channel toxins and pore forming toxins have been characterized. Some ion channel toxins are revealed to be useful tools for biomedical and physiological science. The recent reports showed that sea anemones, including their toxins, are still attractive sources for novel bioactive compounds. This special issue will focus on biological activity, mode of action, ecological significance, isolation and characterization of bioactive compounds including toxins from the sea anemones.

Prof. Dr. Hiroshi Nagai
Guest Editor

Keywords

  • Cnidaria
  • sea anemone
  • biological activity
  • venom
  • toxin
  • bioactive compounds
  • polypeptide

Published Papers (5 papers)

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Research

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Open AccessArticle Functional Expression in Escherichia coli of the Disulfide-Rich Sea Anemone Peptide APETx2, a Potent Blocker of Acid-Sensing Ion Channel 3
Mar. Drugs 2012, 10(7), 1605-1618; doi:10.3390/md10071605
Received: 4 June 2012 / Revised: 18 July 2012 / Accepted: 19 July 2012 / Published: 23 July 2012
Cited by 8 | PDF Full-text (858 KB) | HTML Full-text | XML Full-text
Abstract
Acid-sensing ion channels (ASICs) are proton-gated sodium channels present in the central and peripheral nervous system of chordates. ASIC3 is highly expressed in sensory neurons and plays an important role in inflammatory and ischemic pain. Thus, specific inhibitors of ASIC3 have the [...] Read more.
Acid-sensing ion channels (ASICs) are proton-gated sodium channels present in the central and peripheral nervous system of chordates. ASIC3 is highly expressed in sensory neurons and plays an important role in inflammatory and ischemic pain. Thus, specific inhibitors of ASIC3 have the potential to be developed as novel analgesics. APETx2, isolated from the sea anemone Anthopleura elegantissima, is the most potent and selective inhibitor of ASIC3-containing channels. However, the mechanism of action of APETx2 and the molecular basis for its interaction with ASIC3 is not known. In order to assist in characterizing the ASIC3-APETx2 interaction, we developed an efficient and cost-effective Escherichia coli periplasmic expression system for the production of APETx2. NMR studies on uniformly 13C/15N-labelled APETx2 produced in E. coli showed that the recombinant peptide adopts the native conformation. Recombinant APETx2 is equipotent with synthetic APETx2 at inhibiting ASIC3 channels expressed in Xenopus oocytes. Using this system we mutated Phe15 to Ala, which caused a profound loss of APETx2’s activity on ASIC3. These findings suggest that this expression system can be used to produce mutant versions of APETx2 in order to facilitate structure-activity relationship studies. Full article
(This article belongs to the Special Issue Sea Anemone Toxins)
Open AccessArticle Atypical Reactive Center Kunitz-Type Inhibitor from the Sea Anemone Heteractis crispa
Mar. Drugs 2012, 10(7), 1545-1565; doi:10.3390/md10071545
Received: 18 April 2012 / Revised: 4 July 2012 / Accepted: 11 July 2012 / Published: 19 July 2012
Cited by 5 | PDF Full-text (4790 KB) | HTML Full-text | XML Full-text
Abstract
The primary structure of a new Kunitz-type protease inhibitor InhVJ from the sea anemone Heteractis crispa (Radianthus macrodactylus) was determined by protein sequencing and cDNA cloning. InhVJ amino acid sequence was shown to share high sequence identity (up to 98%) [...] Read more.
The primary structure of a new Kunitz-type protease inhibitor InhVJ from the sea anemone Heteractis crispa (Radianthus macrodactylus) was determined by protein sequencing and cDNA cloning. InhVJ amino acid sequence was shown to share high sequence identity (up to 98%) with the other known Kunitz-type sea anemones sequences. It was determined that the P1 Thr at the reactive site resulted in a decrease of the Ki of InhVJ to trypsin and α-chymotrypsin (7.38 × 10−8 M and 9.93 × 10−7 M, respectively). By structure modeling the functional importance of amino acids at the reactive site as well as at the weak contact site were determined. The significant role of Glu45 for the orientation and stabilization of the InhVJ-trypsin complex was elucidated. We can suggest that there has been an adaptive evolution of the P1 residue at the inhibitor reactive site providing specialization or functional diversification of the paralogs. The appearance of a key so-called P1 Thr residue instead of Lys might lead to refinement of inhibitor specificity in the direction of subfamilies of serine proteases. The absence of Kv channel and TRPV1-receptor modulation activity was confirmed by electrophysiological screening tests. Full article
(This article belongs to the Special Issue Sea Anemone Toxins)
Open AccessArticle Cyclisation Increases the Stability of the Sea Anemone Peptide APETx2 but Decreases Its Activity at Acid-Sensing Ion Channel 3
Mar. Drugs 2012, 10(7), 1511-1527; doi:10.3390/md10071511
Received: 30 May 2012 / Revised: 14 June 2012 / Accepted: 6 July 2012 / Published: 16 July 2012
Cited by 4 | PDF Full-text (613 KB) | HTML Full-text | XML Full-text
Abstract
APETx2 is a peptide isolated from the sea anemone Anthopleura elegantissima. It is the most potent and selective inhibitor of acid-sensing ion channel 3 (ASIC3) and it is currently in preclinical studies as a novel analgesic for the treatment of chronic [...] Read more.
APETx2 is a peptide isolated from the sea anemone Anthopleura elegantissima. It is the most potent and selective inhibitor of acid-sensing ion channel 3 (ASIC3) and it is currently in preclinical studies as a novel analgesic for the treatment of chronic inflammatory pain. As a peptide it faces many challenges in the drug development process, including the potential lack of stability often associated with therapeutic peptides. In this study we determined the susceptibility of wild-type APETx2 to trypsin and pepsin and tested the applicability of backbone cyclisation as a strategy to improve its resistance to enzymatic degradation. Cyclisation with either a six-, seven- or eight-residue linker vastly improved the protease resistance of APETx2 but substantially decreased its potency against ASIC3. This suggests that either the N- or C-terminus of APETx2 is involved in its interaction with the channel, which we confirmed by making N- and C-terminal truncations. Truncation of either terminus, but especially the N-terminus, has detrimental effects on the ability of APETx2 to inhibit ASIC3. The current work indicates that cyclisation is unlikely to be a suitable strategy for stabilising APETx2, unless linkers can be engineered that do not interfere with binding to ASIC3. Full article
(This article belongs to the Special Issue Sea Anemone Toxins)

Review

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Open AccessReview Sea Anemone (Cnidaria, Anthozoa, Actiniaria) Toxins: An Overview
Mar. Drugs 2012, 10(8), 1812-1851; doi:10.3390/md10081812
Received: 31 May 2012 / Revised: 9 July 2012 / Accepted: 25 July 2012 / Published: 22 August 2012
Cited by 49 | PDF Full-text (16456 KB) | HTML Full-text | XML Full-text
Abstract
The Cnidaria phylum includes organisms that are among the most venomous animals. The Anthozoa class includes sea anemones, hard corals, soft corals and sea pens. The composition of cnidarian venoms is not known in detail, but they appear to contain a variety [...] Read more.
The Cnidaria phylum includes organisms that are among the most venomous animals. The Anthozoa class includes sea anemones, hard corals, soft corals and sea pens. The composition of cnidarian venoms is not known in detail, but they appear to contain a variety of compounds. Currently around 250 of those compounds have been identified (peptides, proteins, enzymes and proteinase inhibitors) and non-proteinaceous substances (purines, quaternary ammonium compounds, biogenic amines and betaines), but very few genes encoding toxins were described and only a few related protein three-dimensional structures are available. Toxins are used for prey acquisition, but also to deter potential predators (with neurotoxicity and cardiotoxicity effects) and even to fight territorial disputes. Cnidaria toxins have been identified on the nematocysts located on the tentacles, acrorhagi and acontia, and in the mucous coat that covers the animal body. Sea anemone toxins comprise mainly proteins and peptides that are cytolytic or neurotoxic with its potency varying with the structure and site of action and are efficient in targeting different animals, such as insects, crustaceans and vertebrates. Sea anemones toxins include voltage-gated Na+ and K+ channels toxins, acid-sensing ion channel toxins, Cytolysins, toxins with Kunitz-type protease inhibitors activity and toxins with Phospholipase A2 activity. In this review we assessed the phylogentic relationships of sea anemone toxins, characterized such toxins, the genes encoding them and the toxins three-dimensional structures, further providing a state-of-the-art description of the procedures involved in the isolation and purification of bioactive toxins. Full article
(This article belongs to the Special Issue Sea Anemone Toxins)
Open AccessReview Exploiting the Nephrotoxic Effects of Venom from the Sea Anemone, Phyllodiscus semoni, to Create a Hemolytic Uremic Syndrome Model in the Rat
Mar. Drugs 2012, 10(7), 1582-1604; doi:10.3390/md10071582
Received: 31 May 2012 / Revised: 29 June 2012 / Accepted: 12 July 2012 / Published: 23 July 2012
Cited by 2 | PDF Full-text (5387 KB) | HTML Full-text | XML Full-text
Abstract
In the natural world, there are many creatures with venoms that have interesting and varied activities. Although the sea anemone, a member of the phylum Coelenterata, has venom that it uses to capture and immobilise small fishes and shrimp and for [...] Read more.
In the natural world, there are many creatures with venoms that have interesting and varied activities. Although the sea anemone, a member of the phylum Coelenterata, has venom that it uses to capture and immobilise small fishes and shrimp and for protection from predators, most sea anemones are harmless to man. However, a few species are highly toxic; some have venoms containing neurotoxins, recently suggested as potential immune-modulators for therapeutic application in immune diseases. Phyllodiscus semoni is a highly toxic sea anemone; the venom has multiple effects, including lethality, hemolysis and renal injuries. We previously reported that venom extracted from Phyllodiscus semoni induced acute glomerular endothelial injuries in rats resembling hemolytic uremic syndrome (HUS), accompanied with complement dysregulation in glomeruli and suggested that the model might be useful for analyses of pathology and development of therapeutic approaches in HUS. In this mini-review, we describe in detail the venom-induced acute renal injuries in rat and summarize how the venom of Phyllodiscus semoni could have potential as a tool for analyses of complement activation and therapeutic interventions in HUS. Full article
(This article belongs to the Special Issue Sea Anemone Toxins)

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