In Vitro Cell Sensitivity to Palytoxin Correlates with High Gene Expression of the Na+/K+-ATPase ß2 Subunit Isoform.
Int J Mol Sci
; 21(16)2020 Aug 14.
Article
em En
| MEDLINE
| ID: mdl-32823835
ABSTRACT
The marine polyether palytoxin (PLTX) is one of the most toxic natural compounds, and is involved in human poisonings after oral, inhalation, skin and/or ocular exposure. Epidemiological and molecular evidence suggest different inter-individual sensitivities to its toxic effects, possibly related to genetic-dependent differences in the expression of Na+/K+-ATPase, its molecular target. To identify Na+/K+-ATPase subunits, isoforms correlated with in vitro PLTX cytotoxic potency, sensitivity parameters (EC50 PLTX concentration reducing cell viability by 50%; Emax maximum effect induced by the highest toxin concentration; 10-7 M) were assessed in 60 healthy donors' monocytes by the MTT (methylthiazolyl tetrazolium) assay. Sensitivity parameters, not correlated with donors' demographic variables (gender, age and blood group), demonstrated a high inter-individual variability (median EC50 = 2.7 × 10-10 M, interquartile range 0.4-13.2 × 10-10 M; median Emax = 92.0%, interquartile range 87.5-94.4%). Spearman's analysis showed significant positive correlations between the ß2-encoding ATP1B2 gene expression and Emax values (rho = 0.30; p = 0.025) and between Emax and the ATP1B2/ATP1B3 expression ratio (rho = 0.38; p = 0.004), as well as a significant negative correlation between Emax and the ATP1B1/ATP1B2 expression ratio (rho = -0.30; p = 0.026). This toxicogenetic study represents the first approach to define genetic risk factors that may influence the onset of adverse effects in human PLTX poisonings, suggesting that individuals with high gene expression pattern of the Na+/K+-ATPase ß2 subunit (alone or as ß2/ß1 and/or ß2/ß3 ratio) could be highly sensitive to PLTX toxic effects.
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Base de dados:
MEDLINE
Assunto principal:
Acrilamidas
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Moléculas de Adesão Celular Neuronais
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Regulação da Expressão Gênica
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Venenos de Cnidários
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Adenosina Trifosfatases
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Subunidades Proteicas
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Proteínas de Transporte de Cátions
Tipo de estudo:
Diagnostic_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article