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Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?

Okadaic acid (OA) and its derivatives, which are produced by dinoflagellates of the genera Prorocentrum and Dinophysis, are responsible for diarrhetic shellfish poisoning in humans. In laboratory animals, these toxins cause epithelial damage and fluid accumulation in the gastrointestinal tract, and...

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Autor principal: Munday, Rex
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640535/
https://www.ncbi.nlm.nih.gov/pubmed/23381142
http://dx.doi.org/10.3390/toxins5020267
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author Munday, Rex
author_facet Munday, Rex
author_sort Munday, Rex
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description Okadaic acid (OA) and its derivatives, which are produced by dinoflagellates of the genera Prorocentrum and Dinophysis, are responsible for diarrhetic shellfish poisoning in humans. In laboratory animals, these toxins cause epithelial damage and fluid accumulation in the gastrointestinal tract, and at high doses, they cause death. These substances have also been shown to be tumour promoters, and when injected into the brains of rodents, OA induces neuronal damage reminiscent of that seen in Alzheimer’s disease. OA and certain of its derivatives are potent inhibitors of protein phosphatases, which play many roles in cellular metabolism. In 1990, it was suggested that inhibition of these enzymes was responsible for the diarrhetic effect of these toxins. It is now repeatedly stated in the literature that protein phosphatase inhibition is not only responsible for the intestinal effects of OA and derivatives, but also for their acute toxic effects, their tumour promoting activity and their neuronal toxicity. In the present review, the evidence for the involvement of protein phosphatase inhibition in the induction of the toxic effects of OA and its derivatives is examined, with the conclusion that the mechanism of toxicity of these substances requires re-evaluation.
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spelling pubmed-36405352013-05-03 Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals? Munday, Rex Toxins (Basel) Review Okadaic acid (OA) and its derivatives, which are produced by dinoflagellates of the genera Prorocentrum and Dinophysis, are responsible for diarrhetic shellfish poisoning in humans. In laboratory animals, these toxins cause epithelial damage and fluid accumulation in the gastrointestinal tract, and at high doses, they cause death. These substances have also been shown to be tumour promoters, and when injected into the brains of rodents, OA induces neuronal damage reminiscent of that seen in Alzheimer’s disease. OA and certain of its derivatives are potent inhibitors of protein phosphatases, which play many roles in cellular metabolism. In 1990, it was suggested that inhibition of these enzymes was responsible for the diarrhetic effect of these toxins. It is now repeatedly stated in the literature that protein phosphatase inhibition is not only responsible for the intestinal effects of OA and derivatives, but also for their acute toxic effects, their tumour promoting activity and their neuronal toxicity. In the present review, the evidence for the involvement of protein phosphatase inhibition in the induction of the toxic effects of OA and its derivatives is examined, with the conclusion that the mechanism of toxicity of these substances requires re-evaluation. MDPI 2013-02-04 /pmc/articles/PMC3640535/ /pubmed/23381142 http://dx.doi.org/10.3390/toxins5020267 Text en © 2013 by the authors; licensee MDPI, Basel, Switzerland. http://creativecommons.org/licenses/by/3.0/ This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).
spellingShingle Review
Munday, Rex
Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?
title Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?
title_full Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?
title_fullStr Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?
title_full_unstemmed Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?
title_short Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?
title_sort is protein phosphatase inhibition responsible for the toxic effects of okadaic acid in animals?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3640535/
https://www.ncbi.nlm.nih.gov/pubmed/23381142
http://dx.doi.org/10.3390/toxins5020267
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