Portimine A toxin causes skin inflammation through ZAKα-dependent NLRP1 inflammasome activation

EMBO Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 13, 2025

Abstract In 2020–2021, a “mysterious illness” struck Senegalese fishermen, causing severe acute dermatitis in over one thousand individuals following exposure through drift-net fishing activity. Here, by performing deep analysis of the environmental samples we reveal presence marine dinoflagellate Vulcanodinium rugosum and its associated cyclic imine toxins. Specifically, show that toxin PortimineA, strongly enriched samples, impedes ribosome function human keratinocytes, which subsequently activates stress kinases ZAKα P38 promotes nucleation NLRP1 inflammasome, leading to release IL-1β/IL-18 pro-inflammatory cytokines cell death. Furthermore, cell-based models highlight naturally occurring mutations P38-targeted sites are unable respond PortimineA exposure. Finally, development use organotypic skins zebrafish demonstrate ZAKα-NLRP1 axis drives skin necrosis inflammation. Our results exemplify threats health caused emerging toxins identify NRLP1 as important pharmacological targets mitigate toxicity.

Language: Английский

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First detection of the gymnodimine A isomer, 13-desmethylspirolide D and pinnatoxin G in mussels from Croatia's southern Adriatic Sea

Marine Pollution Bulletin, Journal Year: 2025, Volume and Issue: 215, P. 117888 - 117888

Published: April 4, 2025

Language: Английский

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Detection of the Cyclic Imines Pinnatoxin G, 13-Desmethyl Spirolide C and 20-Methyl Spirolide G in Bivalve Molluscs from Great Britian

Marine Drugs, Journal Year: 2024, Volume and Issue: 22(12), P. 556 - 556

Published: Dec. 12, 2024

Harmful algal biotoxins in the marine environment are a threat to human food safety due their bioaccumulation bivalve shellfish. Whilst official control monitoring provides ongoing risk management for regulated toxins live molluscs, no routine system is currently operation UK other non-regulated toxins. To assess potential presence of such compounds, systematic screen shellfish was conducted throughout Great Britain. A rapid dispersive methanolic extraction used with UHPLC-MS/MS analysis test fifteen cyclic imines and seven brevetoxins 2671 samples taken from designated harvesting areas around Britain during 2018. Out 22 incorporated into method, only pinnatoxin G, 13-desmethyl spirolide C 20-methyl G were detected, maximum concentrations 85.4 µg/kg, 13.4 µg/kg 51.4 respectively. follow up study G-positive examined its esterification fatty acids concluded that following hydrolysis, concentration increased by an average 8.6%, tentative identification these esters determined LC-HRMS. This highlights requirement emerging threats toxicological assessment studies.

Language: Английский

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Investigation of Contamination Levels of CI Toxins in Imported Shellfish Products Available in South Korea

Journal of Food Hygiene and Safety, Journal Year: 2024, Volume and Issue: 39(5), P. 422 - 428

Published: Oct. 30, 2024

Language: Английский

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