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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Endothall thioanhydride inhibits protein phosphatases-1 and -2A in vivo.

The objective of this study was to relate the toxicity of several cantharidin-derivative pesticides with their abilities to inhibit protein phosphatases-1 (PP1) and -2A (PP2A). Cantharidin (CA), endothall, and endothall thioanhydride (ETA) inhibited the activity of PP1 and PP2A, and the potency sequence was CA > endothall > ETA in vitro. We determined the inhibitory potency of these pesticides on hepatic protein phosphatases by administration of the toxins into the portal vein of rats. The potency sequence of ETA > CA > endothall was established for the inhibition of PP1 and PP2A in vivo and shows close correlation with the sequence of relative toxicity. ETA predominantly targets PP1 for inhibition in liver, as revealed by assays specific for PP1 or PP2A. Studies using 3T3 fibroblasts showed that only ETA, but not CA or endothall, induced marked morphological changes. These effects included cell rounding and detachment as well as extensive reorganization of actin filaments and are characteristic for the cell-permeable phosphatase-inhibitory toxins. It is suggested that the in vivo effectiveness is related to enhanced uptake of ETA, because this is permeable across the plasmalemma.[1]


  1. Endothall thioanhydride inhibits protein phosphatases-1 and -2A in vivo. Erdödi, F., Tóth, B., Hirano, K., Hirano, M., Hartshorne, D.J., Gergely, P. Am. J. Physiol. (1995) [Pubmed]
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