Endothall thioanhydride inhibits protein phosphatase 1 and 2a in
vivo.
Erddi, Ferenc, B[acute]ela T[acute]oth, Katsuya Hirano, Mayumi Hirano,
David J. Hartshorne, and P[acute]al Gergely.
Department of Medical Chemistry, University Medical School of
Debrecen, H-4026 Debrecen, Hungary; Muscle Biology Group, University
of Arizona, Tucson AZ 85721, USA
APStracts 2:0203C, 1995.
The objective of this study was to relate the toxicity of several
cantharidin derivative pesticides with their abilities to inhibit
protein phosphatase 1 (PP1) and 2A (PP2A). Cantharidin (CA),
endothall (ET) and endothall thioanhydride (ETA) inhibited the
activity of PP1 and PP2A and the potency sequence was CA>ET>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>ET was
established for the inhibition of PP1 and PP2A in vivo that 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 fibroblast showed
that only ETA, but not CA or ET induced marked morphological changes.
These effects included cell rounding, detachment and 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, since
this is permeable across the plasmalemma.
Received 6 March 1995; accepted in final form 11 May 1995.
APS Manuscript Number C123-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 26 May 1995.