Relationship of tri-O-cresyl phosphate-induced delayed neurotoxicity to enhancement of in vitro phosphorylation of hen brain and spinal cord proteins.
Enhancement of endogenous kinase-dependent in vitro protein phosphorylation of subcellular fractions from brains and spinal cords of hens paralyzed 3 weeks after intoxication with tri-o-cresyl phosphate was correlated with the development of organophosphorus compound-induced delayed neurotoxicity (OPIDN). This was documented by showing: parallel dose-dependence curves for both responses, phosphorylation enhancement in proteins from hens treated with OPIDN-producing O-4-bromo-2,5-dichlorophenyl-O-methyl phenylphosphonothioates, but not in those treated with non-OPIDN-producing O,O-diethyl-O-4-nitrophenyl phosphorothioate or tri-p-cresyl phosphate, and shared age and species selectivities for both effects. These results strengthen our earlier observation of a close temporal relationship between protein phosphorylation enhancement and OPIDN. Further studies suggest that the proximate cause of the enhanced phosphorylation is not related to an alteration in protein phosphatase activity or to the preservation of a rate-limiting pool of [gamma-32P]ATP by adenosine triphosphatase inhibition. Therefore, it is most likely related either to altered protein kinase activity or amount (due to chemically originated physical disruption of the neuron). These data support the hypothesis that increased protein phosphorylation may be involved in the development of OPIDN.
Patton, SE; Lapadula, DM; Abou-Donia, MB
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