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

Abstract

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.

Keywords::

• Soman
• warfare agent
• protein kinase C (PKC)
• immunoreactivity
• neurotoxicity

Acknowledgements

The authors are thankful for the extraordinary support and extending facility given by Dr R. Vijayaraghavan, Ph. D, Director, Defence Research and Development (DRDE), Ministry of Defence, Government of India, which made this research possible.

Declaration of interest

The authors report no conflict of interest.