Soman-induced alterations of protein kinase C isozymes expression in five discrete areas of the rat brain.

Drug Chem Toxicol

Biochemistry Division, Defense Research and Development Establishment, Gwalior, India.

Published: July 2011

Soman is a highly neurotoxic chemical warfare agent and inhibits the neural enzyme, acetylcholinesterase (AChE). Protein kinase C (PKC) isozymes regulate a wide range of cellular functions to a variety of extracellular stimuli. However, their exact role in nerve-agent poisoning is not well understood. In the present study, we investigated the effect of soman (80 μg/kg⁻¹, administered subcutaneously) on two PKC isozymes' immunoreactivity levels and activities of PKC and AChE in different rat-brain areas. Results showed a significant induction in PKC βII and ζ isoenzyme expression levels from 2.5 hours to 14 days post-soman exposure periods in the hippocampus, cerebellum, thalamus and cerebral cortex. The striatum showed reduced expression levels of both the isozymes from 1 to 3 days after soman exposure. PKC activity was increased in the cerebrum and cerebellum up to 7 days post-soman exposure. The toxicity target enzyme, AChE activity remained inhibited in plasma and brain up to 3 days post exposure and thereafter recovered to control levels. The results suggest a possible role of PKC isozymes in nerve-agent-induced neurotoxicity.

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Source
http://dx.doi.org/10.3109/01480545.2010.511647DOI Listing

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