Differences in Toxic Response Induced by Three Variants of the Diarrheic Shellfish Poisoning Phycotoxins in Human Intestinal Epithelial Caco-2 Cells

Autor: Antoine Huguet, Hélène Quenault, Valérie Fessard, Fanny Rousselet, Olivia Drapeau
Přispěvatelé: Laboratoire de Fougères - ANSES, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire de Ploufragan-Plouzané-Niort [ANSES]
Jazyk: angličtina
Rok vydání: 2020
Předmět:
MAPK/ERK pathway
intoxication diarrhéique par les mollusques
Cell Survival
Health
Toxicology and Mutagenesis
phycotoxine
Phosphatase
lcsh:Medicine
Toxicology
medicine.disease_cause
diarrheic shellfish poisoning
Article
Microbiology
Transcriptome
03 medical and health sciences
chemistry.chemical_compound
transcriptomics
0302 clinical medicine
mollusque
phycotoxins
okadaic acid
medicine
toxicité
Animals
Humans
Shellfish Poisoning
caco-2 cell
Intestinal Mucosa
acideokadaique
Dinophysistoxin
030304 developmental biology
0303 health sciences
Dose-Response Relationship
Drug
Toxin
transcriptomique
lcsh:R
toxicity
Protein phosphatase 2
Okadaic acid
3. Good health
chemistry
Caco-2
[SDV.TOX]Life Sciences [q-bio]/Toxicology
030220 oncology & carcinogenesis
Toxicity
Marine Toxins
Caco-2 Cells
toxine marine
Zdroj: Toxins
Toxins, MDPI, 2020, 12 (12), pp.783. ⟨10.3390/toxins12120783⟩
Volume 12
Issue 12
Toxins, Vol 12, Iss 783, p 783 (2020)
ISSN: 2072-6651
Popis: International audience; Diarrheic shellfish poisoning (DSP) is caused by the consumption of shellfish contaminated with a group of phycotoxins that includes okadaic acid (OA), dinophysistoxin-1 (DTX-1), and dinophysistoxin-2 (DTX-2). These toxins are inhibitors of serine/threonine protein phosphatases 1 (PP1) and 2A (PP2A), but show distinct levels of toxicity. Aside from a difference in protein phosphatases (PP) inhibition potency that would explain these differences in toxicity, others mechanisms of action are thought to be involved. Therefore, we investigated and compared which mechanisms are involved in the toxicity of these three analogues. As the intestine is one of the target organs, we studied the transcriptomic profiles of human intestinal epithelial Caco-2 cells exposed to OA, DTX-1, and DTX-2. The pathways specifically affected by each toxin treatment were further confirmed through the expression of key genes and markers of toxicity. Our results did not identify any distinct biological mechanism for OA and DTX-2. However, only DTX-1 induced up-regulation of the MAPK transduction signalling pathway, and down-regulation of gene products involved in the regulation of DNA repair. As a consequence, based on transcriptomic results, we demonstrated that the higher toxicity of DTX-1 compared to OA and DTX-2 was consistent with certain specific pathways involved in intestinal cell response.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje