Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 

Saved Queries

Sign in to use this feature.

Search Filter Reset All

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
Add Subjects Reset
Select Subjects

Journals

remove_circle_outline
Add Journals Reset
Select Journals

Article Types

remove_circle_outline
remove_circle_outline
Add Article Types Reset
Select Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
Add Countries / Regions Reset
Select Countries / Regions
Update Search
share announcement

Search Results (4)

Search Parameters:
Keywords = APETx-like toxins

Order results
Result details
Results per page
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
20 pages, 2899 KiB  
Article
Anxiolytic, Analgesic and Anti-Inflammatory Effects of Peptides Hmg 1b-2 and Hmg 1b-4 from the Sea Anemone Heteractis magnifica
by Irina N. Gladkikh, Anna A. Klimovich, Rimma S. Kalina, Yulia V. Kozhevnikova, Timur A. Khasanov, Dmitry I. Osmakov, Sergey G. Koshelev, Margarita M. Monastyrnaya, Yaroslav A. Andreev, Elena V. Leychenko and Sergey A. Kozlov
Toxins 2023, 15(5), 341; https://doi.org/10.3390/toxins15050341 - 15 May 2023
Cited by 6 | Viewed by 2830
Abstract
Acid-sensing ion channels (ASICs) have been known as sensors of a local pH change within both physiological and pathological conditions. ASIC-targeting peptide toxins could be potent molecular tools for ASIC-manipulating in vitro, and for pathology treatment in animal test studies. Two sea anemone [...] Read more.
Acid-sensing ion channels (ASICs) have been known as sensors of a local pH change within both physiological and pathological conditions. ASIC-targeting peptide toxins could be potent molecular tools for ASIC-manipulating in vitro, and for pathology treatment in animal test studies. Two sea anemone toxins, native Hmg 1b-2 and recombinant Hmg 1b-4, both related to APETx-like peptides, inhibited the transient current component of human ASIC3-Δ20 expressed in Xenopus laevis oocytes, but only Hmg 1b-2 inhibited the rat ASIC3 transient current. The Hmg 1b-4 action on rASIC3 as a potentiator was confirmed once again. Both peptides are non-toxic molecules for rodents. In open field and elevated plus maze tests, Hmg 1b-2 had more of an excitatory effect and Hmg 1b-4 had more of an anxiolytic effect on mouse behavior. The analgesic activity of peptides was similar and comparable to diclofenac activity in an acid-induced muscle pain model. In models of acute local inflammation induced by λ-carrageenan or complete Freund’s adjuvant, Hmg 1b-4 had more pronounced and statistically significant anti-inflammatory effects than Hmg 1b-2. It exceeded the effect of diclofenac and, at a dose of 0.1 mg/kg, reduced the volume of the paw almost to the initial volume. Our data highlight the importance of a comprehensive study of novel ASIC-targeting ligands, and in particular, peptide toxins, and present the slightly different biological activity of the two similar toxins. Full article
(This article belongs to the Special Issue Ion Channels, Venom, and Toxins)
►▼ Show Figures

Figure 1

40 pages, 4004 KiB  
Review
Mechanisms of Action of the Peptide Toxins Targeting Human and Rodent Acid-Sensing Ion Channels and Relevance to Their In Vivo Analgesic Effects
by Clément Verkest, Miguel Salinas, Sylvie Diochot, Emmanuel Deval, Eric Lingueglia and Anne Baron
Toxins 2022, 14(10), 709; https://doi.org/10.3390/toxins14100709 - 17 Oct 2022
Cited by 21 | Viewed by 5296
Abstract
Acid-sensing ion channels (ASICs) are voltage-independent H+-gated cation channels largely expressed in the nervous system of rodents and humans. At least six isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) associate into homotrimers or heterotrimers to form functional channels with highly [...] Read more.
Acid-sensing ion channels (ASICs) are voltage-independent H+-gated cation channels largely expressed in the nervous system of rodents and humans. At least six isoforms (ASIC1a, 1b, 2a, 2b, 3 and 4) associate into homotrimers or heterotrimers to form functional channels with highly pH-dependent gating properties. This review provides an update on the pharmacological profiles of animal peptide toxins targeting ASICs, including PcTx1 from tarantula and related spider toxins, APETx2 and APETx-like peptides from sea anemone, and mambalgin from snake, as well as the dimeric protein snake toxin MitTx that have all been instrumental to understanding the structure and the pH-dependent gating of rodent and human cloned ASICs and to study the physiological and pathological roles of native ASICs in vitro and in vivo. ASICs are expressed all along the pain pathways and the pharmacological data clearly support a role for these channels in pain. ASIC-targeting peptide toxins interfere with ASIC gating by complex and pH-dependent mechanisms sometimes leading to opposite effects. However, these dual pH-dependent effects of ASIC-inhibiting toxins (PcTx1, mambalgin and APETx2) are fully compatible with, and even support, their analgesic effects in vivo, both in the central and the peripheral nervous system, as well as potential effects in humans. Full article
(This article belongs to the Special Issue Toxins: Mr Hyde or Dr Jekyll?)
►▼ Show Figures

Figure 1

20 pages, 4203 KiB  
Article
Nicotinic Acetylcholine Receptors Are Novel Targets of APETx-like Toxins from the Sea Anemone Heteractis magnifica
by Rimma S. Kalina, Igor E. Kasheverov, Sergey G. Koshelev, Oksana V. Sintsova, Steve Peigneur, Ernesto Lopes Pinheiro-Junior, Roman S. Popov, Victoria E. Chausova, Margarita M. Monastyrnaya, Pavel S. Dmitrenok, Marina P. Isaeva, Jan Tytgat, Sergey A. Kozlov, Emma P. Kozlovskaya, Elena V. Leychenko and Irina N. Gladkikh
Toxins 2022, 14(10), 697; https://doi.org/10.3390/toxins14100697 - 11 Oct 2022
Cited by 8 | Viewed by 2715
Abstract
The nicotinic acetylcholine receptors (nAChRs) are prototypical ligand-gated ion channels, provide cholinergic signaling, and are modulated by various venom toxins and drugs in addition to neurotransmitters. Here, four APETx-like toxins, including two new toxins, named Hmg 1b-2 Metox and Hmg 1b-5, were [...] Read more.
The nicotinic acetylcholine receptors (nAChRs) are prototypical ligand-gated ion channels, provide cholinergic signaling, and are modulated by various venom toxins and drugs in addition to neurotransmitters. Here, four APETx-like toxins, including two new toxins, named Hmg 1b-2 Metox and Hmg 1b-5, were isolated from the sea anemone Heteractis magnifica and characterized as novel nAChR ligands and acid-sensing ion channel (ASIC) modulators. All peptides competed with radiolabeled α-bungarotoxin for binding to Torpedo californica muscle-type and human α7 nAChRs. Hmg 1b-2 potentiated acetylcholine-elicited current in human α7 receptors expressed in Xenopus laevis oocytes. Moreover, the multigene family coding APETx-like peptides library from H. magnifica was described and in silico surface electrostatic potentials of novel peptides were analyzed. To explain the 100% identity of some peptide isoforms between H. magnifica and H. crispa, 18S rRNA, COI, and ITS analysis were performed. It has been shown that the sea anemones previously identified by morphology as H. crispa belong to the species H. magnifica. Full article
(This article belongs to the Special Issue Ion Channels, Venom, and Toxins)
►▼ Show Figures

Figure 1

18 pages, 2581 KiB  
Article
APETx-Like Peptides from the Sea Anemone Heteractis crispa, Diverse in Their Effect on ASIC1a and ASIC3 Ion Channels
by Rimma S. Kalina, Sergey G. Koshelev, Elena A. Zelepuga, Natalia Y. Kim, Sergey A. Kozlov, Emma P. Kozlovskaya, Margarita M. Monastyrnaya and Irina N. Gladkikh
Toxins 2020, 12(4), 266; https://doi.org/10.3390/toxins12040266 - 20 Apr 2020
Cited by 15 | Viewed by 5824
Abstract
Currently, five peptide modulators of acid-sensing ion channels (ASICs) attributed to structural class 1b of sea anemone toxins have been described. The APETx2 toxin is the first and most potent ASIC3 inhibitor, so its homologs from sea anemones are known as the APETx-like [...] Read more.
Currently, five peptide modulators of acid-sensing ion channels (ASICs) attributed to structural class 1b of sea anemone toxins have been described. The APETx2 toxin is the first and most potent ASIC3 inhibitor, so its homologs from sea anemones are known as the APETx-like peptides. We have discovered that two APETx-like peptides from the sea anemone Heteractis crispa, Hcr 1b-3 and Hcr 1b-4, demonstrate different effects on rASIC1a and rASIC3 currents. While Hcr 1b-3 inhibits both investigated ASIC subtypes with IC50 4.95 ± 0.19 μM for rASIC1a and 17 ± 5.8 μM for rASIC3, Hcr 1b-4 has been found to be the first potentiator of ASIC3, simultaneously inhibiting rASIC1a at similar concentrations: EC50 1.53 ± 0.07 μM and IC50 1.25 ± 0.04 μM. The closest homologs, APETx2, Hcr 1b-1, and Hcr 1b-2, previously demonstrated the ability to inhibit hASIC3 with IC50 63 nM, 5.5, and 15.9 μM, respectively, while Hcr 1b-2 also inhibited rASIC1a with IC50 4.8 ± 0.3 μM. Computer modeling allowed us to describe the peculiarities of Hcr 1b-2 and Hcr 1b-4 interfaces with the rASIC1a channel and the stabilization of the expanded acidic pocket resulting from peptides binding which traps the rASIC1a channel in the closed state. Full article
(This article belongs to the Special Issue Sea Anemone Venom)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying article 1-50 on page 1 of 1.
Back to TopTop