Interrogating stonefish venom: small molecules present in envenomation caused by Synanceia spp.
The stonefish Synanceia verrucosa and Synanceia horrida are arguably the most venomous fish species on earth and the culprits of severe stings in humans globally. Investigation into the venoms of these two species has mainly focused on protein composition, in an attempt to identify the most medicall...
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| Format: | Article |
| Language: | English |
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Wiley
2025-03-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.13926 |
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| author | Silvia Luiza Saggiomo Steve Peigneur Jan Tytgat Norelle L. Daly David Thomas Wilson |
| author_facet | Silvia Luiza Saggiomo Steve Peigneur Jan Tytgat Norelle L. Daly David Thomas Wilson |
| author_sort | Silvia Luiza Saggiomo |
| collection | DOAJ |
| description | The stonefish Synanceia verrucosa and Synanceia horrida are arguably the most venomous fish species on earth and the culprits of severe stings in humans globally. Investigation into the venoms of these two species has mainly focused on protein composition, in an attempt to identify the most medically relevant proteins, such as the lethal verrucotoxin and stonustoxin components. This study, however, focused on medically relevant small molecules, and through nuclear magnetic resonance, mass spectroscopy, and fractionation techniques, we discovered and identified the presence of three molecules new to stonefish venom, namely γ‐aminobutyric acid (GABA), choline and 0‐acetylcholine, and provide the first report of GABA identified in a fish venom. Analysis of the crude venoms on human nicotinic acetylcholine receptors (nAChRs) and a GABAA receptor (GABAAR) showed S. horrida venom could activate neuronal (α7) and adult muscle‐type (α1β1δε) nAChRs, while both crude S. horrida and S. verrucosa venoms activated the GABAAR (α1β2γ2). Cytotoxicity studies in immunologically relevant cells (human PBMCs) indicated the venoms possess cell‐specific cytotoxicity and analysis of the venom fractions on Na+ channel subtypes involved in pain showed no activity. This work highlights the need to further investigate the small molecules found in venoms to help understand the mechanistic pathways of clinical symptoms for improved treatment of sting victims, in addition to the discovery of potential drug leads. |
| format | Article |
| id | doaj-art-58f91bf3a1664757bf081b68ee60b31e |
| institution | DOAJ |
| issn | 2211-5463 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Wiley |
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| spelling | doaj-art-58f91bf3a1664757bf081b68ee60b31e2025-08-20T02:58:00ZengWileyFEBS Open Bio2211-54632025-03-0115339941410.1002/2211-5463.13926Interrogating stonefish venom: small molecules present in envenomation caused by Synanceia spp.Silvia Luiza Saggiomo0Steve Peigneur1Jan Tytgat2Norelle L. Daly3David Thomas Wilson4Australian Institute of Tropical Health and Medicine James Cook University Cairns AustraliaToxicology and Pharmacology Katholieke Universiteit (KU) Leuven BelgiumToxicology and Pharmacology Katholieke Universiteit (KU) Leuven BelgiumAustralian Institute of Tropical Health and Medicine James Cook University Cairns AustraliaAustralian Institute of Tropical Health and Medicine James Cook University Cairns AustraliaThe stonefish Synanceia verrucosa and Synanceia horrida are arguably the most venomous fish species on earth and the culprits of severe stings in humans globally. Investigation into the venoms of these two species has mainly focused on protein composition, in an attempt to identify the most medically relevant proteins, such as the lethal verrucotoxin and stonustoxin components. This study, however, focused on medically relevant small molecules, and through nuclear magnetic resonance, mass spectroscopy, and fractionation techniques, we discovered and identified the presence of three molecules new to stonefish venom, namely γ‐aminobutyric acid (GABA), choline and 0‐acetylcholine, and provide the first report of GABA identified in a fish venom. Analysis of the crude venoms on human nicotinic acetylcholine receptors (nAChRs) and a GABAA receptor (GABAAR) showed S. horrida venom could activate neuronal (α7) and adult muscle‐type (α1β1δε) nAChRs, while both crude S. horrida and S. verrucosa venoms activated the GABAAR (α1β2γ2). Cytotoxicity studies in immunologically relevant cells (human PBMCs) indicated the venoms possess cell‐specific cytotoxicity and analysis of the venom fractions on Na+ channel subtypes involved in pain showed no activity. This work highlights the need to further investigate the small molecules found in venoms to help understand the mechanistic pathways of clinical symptoms for improved treatment of sting victims, in addition to the discovery of potential drug leads.https://doi.org/10.1002/2211-5463.13926acetylcholineGABAstonefishSynanceiavenom |
| spellingShingle | Silvia Luiza Saggiomo Steve Peigneur Jan Tytgat Norelle L. Daly David Thomas Wilson Interrogating stonefish venom: small molecules present in envenomation caused by Synanceia spp. FEBS Open Bio acetylcholine GABA stonefish Synanceia venom |
| title | Interrogating stonefish venom: small molecules present in envenomation caused by Synanceia spp. |
| title_full | Interrogating stonefish venom: small molecules present in envenomation caused by Synanceia spp. |
| title_fullStr | Interrogating stonefish venom: small molecules present in envenomation caused by Synanceia spp. |
| title_full_unstemmed | Interrogating stonefish venom: small molecules present in envenomation caused by Synanceia spp. |
| title_short | Interrogating stonefish venom: small molecules present in envenomation caused by Synanceia spp. |
| title_sort | interrogating stonefish venom small molecules present in envenomation caused by synanceia spp |
| topic | acetylcholine GABA stonefish Synanceia venom |
| url | https://doi.org/10.1002/2211-5463.13926 |
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