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Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?
AgResearch Ltd, Ruakura Research Centre, Private Bag 3123, Hamilton, New Zealand
Received: 6 November 2012; in revised form: 8 January 2013 / Accepted: 24 January 2013 / Published: 4 February 2013
Abstract: 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.
Keywords: okadaic acid toxicity; protein phosphatase inhibition
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MDPI and ACS Style
Munday, R. Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals? Toxins 2013, 5, 267-285.
Munday R. Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals? Toxins. 2013; 5(2):267-285.
Munday, Rex. 2013. "Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?" Toxins 5, no. 2: 267-285.