Disease relevance of Hydout

• Inhibition of PP2A activity may account for the diverse effects and toxicity of cantharidin and its analogs, including the herbicide endothall, in mammals and possibly plants [1].
• Thus, endothall inhibits preferentially HCC growth and these new rat hepatocellular carcinoma lines may be useful for further biochemical and pharmacological studies on PP2A inhibitors, and for testing new forms of treatment of hepatic cell carcinomas [2].

High impact information on Hydout

• In an in vitro assay, purified PP2A(c) dephosphorylated a GST-NHE1 fusion protein containing aa 625-747 of the NHE1 regulatory domain, which had been pre-phosphorylated by recombinant RSK; such dephosphorylation was inhibited by the PP2A-selective phosphatase inhibitor endothall [3].
• In intact ARVM, the ability of CPA to attenuate the phenylephrine-induced increase in NHE1 phosphorylation and activity was lost in the presence of endothall [3].
• Either RRAT or RGET was sufficient for PKA activation of hClC-2 at pH(o) 7.4, as long as phosphatase inhibitors (cyclosporin A or endothal) were present [4].
• This down-regulation of the cyt path likely requires events outside the mitochondrion and is effectively blocked by cantharidin or endothall, indicating that protein dephosphorylation is one critical process involved [5].
• We used endothall (ET) as a cell-permeable inhibitor of serine/threonine-specific protein phosphatases to alter cytological and biochemical characteristics of cell division in cultured alfalfa cells [6].

Biological context of Hydout

• The toxicity of the herbicide endothal (exo,exo-7-oxabicyclo[2.2.1]heptane-2,3-dicarboxylic acid) to mice (ip LD50 = 14 mg/kg) is attributed to the inhibition of protein phosphatase 2A (PP2A) at the cantharidin binding site [7].
• The [3H]ETA binding site of liver cytosol is inhibited 75-80% by LD50 doses of 2,3-dimethylendothall anhydride and thioanhydride but only 24% by an LD50 dose of endothall thioanhydride, with assays 30 min after ip treatment.(ABSTRACT TRUNCATED AT 250 WORDS)[8]
• Endothal (1diacid) and [3H]cantharidic acid ([3H]CA) bind with high affinity to the catalytic subunit of protein phosphatase 2A (PP2A) [9].

Anatomical context of Hydout

• Studies using 3T3 fibroblasts showed that only ETA, but not CA or endothall, induced marked morphological changes [10].

Associations of Hydout with other chemical compounds

• CA and the herbicide endothall also inhibited spinach leaf PP1 and PP2A and, at 50 microM, decreased the PP2A-mediated light-induced activation of nitrate reductase in intact spinach leaves by 62 and 56%, respectively [11].
• The OsPR1a gene was found to be cut-inducible, whereas the phytohormones JA, salicylic acid (SA), 3-indoleacetic acid, gibberellin, and ethylene (using ethylene generator ethephon, ET) enhanced accumulation of OsPR1a transcript, as well as the protein phosphatase inhibitors cantharidin (CN) and endothall (EN) [12].
• PP2A in liver cytosol was greatly stabilized with 30% glycerol as a preliminary step in the potential use of endothal-type derivatives for affinity chromatography [9].
• Half maximal inhibition of PP2Ac was achieved at 0.3 nM okadaic acid, 0.1 nM microcystin-LR, 56 nM cantharidin and 280 nM endothall concentrations [13].

Gene context of Hydout

• CA and three analogues (cantharidic acid, palasonin and endothall) inhibited PP2A and protein phosphatase 1 (PP1) but not PP2B or PP2C [11].
• 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 [10].
• All compounds inhibited PP activity in homogenates of rat aorta with a rank order of potency of Cant = cantharidic acid > endothall [14].
• Interestingly the protein phosphatase (PP) inhibitors, cantharidin, endothall, and okadaic acid, rapidly and potently up-regulated the JIOsPR10 expression, suggesting involvement of the phosphorylation/dephosphorylation events [15].
• On the cardiac contractile, electrophysiological and biochemical effects of endothall, a protein phosphatase inhibitor [16].

References