Nicotinic Acetylcholine Receptors Are Novel Targets of APETx-like Toxins from the Sea Anemone Heteractis magnifica

Kalina, Rimma; Kasheverov, Igor E.; Koshelev, Sergey G.; Sintsova, Oksana; Peigneur, Steve; Pinheiro-Júnior, Ernesto Lopes; Popov, Roman S.; Chausova, Victoria; Monastyrnaya, Margarita; Dmitrenok, Pavel S.; Isaeva, Marina; Tytgat, Jan; Kozlov, Sergey A.; Kozlovskaya, É. P.; Leychenko, Elena

doi:10.3390/toxins14100697

Cited by 7 publications

(5 citation statements)

References 73 publications

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“…The samples of sea anemone Heteractis magnifica, designated as 91, 116, and 146, were collected from the South China Sea (Gulf of Siam) near Nam Du Islands, ( C before use. The identity of the species was confirmed by phylogenetic analysis of 18S rRNA, COI, and ITS sequences, as was reported recently for an H. magnifica sample [13].…”

Section: Collection and Identification Of Sea Anemone Samplessupporting

confidence: 81%

Bioprospecting of Sea Anemones (Cnidaria, Anthozoa, Actiniaria) for β-Defensin-like α-Amylase Inhibitors

Popkova,

Otstavnykh,

Sintsova

et al. 2023

Biomedicines

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Diabetes mellitus is one of the most serious diseases of our century. The drugs used are limited or have serious side effects. The search for new sources of compounds for effective treatment is relevant. Magnificamide, a peptide inhibitor of mammalian α-amylases, isolated from the venom of sea anemone Heteractis magnifica, can be used for the control of postprandial hyperglycemia in diabetes mellitus. Using the RACE approach, seven isoforms of magnificamide were detected in H. magnifica tentacles. The exon–intron structure of magnificamide genes was first established, and intron retention in the mature peptide-encoding region was revealed. Additionally, an α-amylase inhibitory domain was discovered in the mucins of some sea anemones. According to phylogenetics, sea anemones diverge into two groups depending on the presence of β-defensin-like α-amylase inhibitors and/or mucin-inhibitory domains. It is assumed that the intron retention phenomenon leads to additional diversity in the isoforms of inhibitors and allows for its neofunctionalization in sea anemone tentacles. Bioprospecting of sea anemones of the order Actiniaria for β-defensin-like α-amylase inhibitors revealed a diversity of inhibitory sequences that represents a starting point for the design of effective glucose-lowering drugs.

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Section: Collection and Identification Of Sea Anemone Samplessupporting

confidence: 81%

Bioprospecting of Sea Anemones (Cnidaria, Anthozoa, Actiniaria) for β-Defensin-like α-Amylase Inhibitors

Popkova,

Otstavnykh,

Sintsova

et al. 2023

Biomedicines

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“…The Hmg 1b-2 and Hmg 1b-4 (originally named Hcr 1b-4) peptides differed in their selectivity to ion channels: the second one has been found to be a potentiator of ASIC3 and inhibitor of ASIC1a at similar concentrations—EC 50 1.53 ± 0.07 μM and IC 50 1.25 ± 0.04 μM [ 137 ]. Hmg 1b-2 (originally named Hcr 1b-2) was an inhibitor of both ASIC3 with IC 50 15.9 μM and ASIC1a with IC 50 4.8 ± 0.3 μM, but at a concentration of 1 µM, it potentiated ACh-elicited currents of both α7 and α1β1δε nAChRs [ 137 , 138 , 139 ]. Then, a few novel (see Section 2 ) nAChR-targeting peptides from the Metridium senile sea anemone were discovered at IBCh and structurally and functionally characterized in collaboration with Chinese and Norwegian colleagues [ 21 ] ( Figure 1 and Figure 2 E).…”

Section: Marine Toxins Acting On the Ligand- Or Voltage-gated Ion Cha...mentioning

confidence: 99%

Fifty Years of Animal Toxin Research at the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry RAS

Tsetlin,

Shelukhina,

Kozlov

et al. 2023

IJMS

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This review covers briefly the work carried out at our institute (IBCh), in many cases in collaboration with other Russian and foreign laboratories, for the last 50 years. It discusses the discoveries and studies of various animal toxins, including protein and peptide neurotoxins acting on the nicotinic acetylcholine receptors (nAChRs) and on other ion channels. Among the achievements are the determination of the primary structures of the α-bungarotoxin-like three-finger toxins (TFTs), covalently bound dimeric TFTs, glycosylated cytotoxin, inhibitory cystine knot toxins (ICK), modular ICKs, and such giant molecules as latrotoxins and peptide neurotoxins from the snake, as well as from other animal venoms. For a number of toxins, spatial structures were determined, mostly by 1H-NMR spectroscopy. Using this method in combination with molecular modeling, the molecular mechanisms of the interactions of several toxins with lipid membranes were established. In more detail are presented the results of recent years, among which are the discovery of α-bungarotoxin analogs distinguishing the two binding sites in the muscle-type nAChR, long-chain α-neurotoxins interacting with α9α10 nAChRs and with GABA-A receptors, and the strong antiviral effects of dimeric phospholipases A2. A summary of the toxins obtained from arthropod venoms includes only highly cited works describing the molecules’ success story, which is associated with IBCh. In marine animals, versatile toxins in terms of structure and molecular targets were discovered, and careful work on α-conotoxins differing in specificity for individual nAChR subtypes gave information about their binding sites.

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“…isolated from soda-like showed promising anticancer activity against breast cancer MDA-MB-231 cells. Sea anemone and its associated bacteria produce various toxins, bacteriocins, enzymes, and peptides and they can fight against various cancer 25,26,27 . This could be the reason for the promising result of anticancer activity using sea anemones-associated bacteria in this study.…”

Section: In Vitro Anticancer Assaymentioning

confidence: 99%

Isolation and Characterization of Anticancer Compound Producing Marine Paenibacillus lentimorbus SAGM 3 Collected from a Sea Anemone, Heteractis species

Vinothkumar

Pugalendhi

2023

Biosci., Biotech. Res. Asia

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Sea anemone-associated bacteria were considered promising candidates for the synthesis of many novel bioactive compounds. Thus culturable symbiotic bacteria that exist in the sea anemones met much attention when compared to other benthic marine dwellers. In this study, an attempt was made to explore the anticancer potentials of symbiotic bacteria isolated from a sea anemone, Heteractis species. Nine symbiotic bacteria were isolated, pure cultured and screened for their anticancer potential using two breast cancer cell lines. Among the strains, SAGM 3 showed appreciable growth inhibition activity of 43.1% and 47.1% against the studied cell lines, viz. MCF7 and MDA-MB-231 and this strain was selected for further studies. Based on the 16S rRNA molecular profiling, the SAGM 3 isolate was noted as Paenibacillus lentimorbus and the sequence of SAGM 3 was deposited in GeneBank with the accession number MW737456.1. During the growth kinetics profiling, maximum bacterial growth rate and anticancer activities were recorded from 60 to 96 hrs of incubation. The present investigation provides baseline data understanding the pharmaceutical significance of a symbiotic marine bacterium procured from the sea anemone, Heteractis species.

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Nicotinic Acetylcholine Receptors Are Novel Targets of APETx-like Toxins from the Sea Anemone Heteractis magnifica

Cited by 7 publications

References 73 publications

Bioprospecting of Sea Anemones (Cnidaria, Anthozoa, Actiniaria) for β-Defensin-like α-Amylase Inhibitors

Bioprospecting of Sea Anemones (Cnidaria, Anthozoa, Actiniaria) for β-Defensin-like α-Amylase Inhibitors

Fifty Years of Animal Toxin Research at the Shemyakin–Ovchinnikov Institute of Bioorganic Chemistry RAS

Isolation and Characterization of Anticancer Compound Producing Marine Paenibacillus lentimorbus SAGM 3 Collected from a Sea Anemone, Heteractis species

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