Hepatocyte deformation induced by cyanobacterial toxins reflects inhibition of protein phosphatases

John Eriksson, Diana Toivola, Jussi Meriluoto, H Karaki, YG Han, D Hartshorne

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    Abstract

    The cyclic peptide hepatotoxins microcystin-LR, 7-desmethyl-microcystin-RR and nodularin are potent inhibitors of the protein phosphatases type 1 and type 2A. Their potency of inhibition resembles calyculin-A and to a lesser extent okadaic acid. These hepatotoxins increase the overall level of protein phosphorylation in hepatocytes. Evidence is presented to indicate that in hepatocytes the morphological changes and effects on the cytoskeleton are due to phosphatase inhibition. The potency of these compounds in inducing hepatocyte deformation is similar to their potency in inhibiting phosphatase activity. These results suggest that the hepatotoxicity of these peptides is related to inhibition of phosphatases, and further indicate the importance of the protein phosphorylation in maintenance of structural and homeostatic integrity in these cells.
    Original languageUndefined/Unknown
    Pages (from-to)1347–1353
    JournalBiochemical and Biophysical Research Communications
    Volume173
    Issue number3
    Publication statusPublished - 1990
    MoE publication typeA1 Journal article-refereed

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