title: 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.
authors.affiliation: Biochemistry Division, Defense Research and Development Establishment, Gwalior, India.
authors.forename: Golime
authors.initials: G
authors.lastname: RamaRao
authors.forename: Chandrakant
authors.initials: C
authors.lastname: Waghmare
authors.forename: Arvind
authors.initials: A
authors.lastname: Kumar Gupta
authors.forename: Bijoy Krishna
authors.initials: BK
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002619:Chemical Warfare Agents / Q000633:toxicity*; D002802:Cholinesterases / Q000097:blood / Q000378:metabolism; D005260:Female; D007527:Isoenzymes; D011493:Protein Kinase C / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000633:toxicity*
chemical_list: D002619:Chemical Warfare Agents; D007527:Isoenzymes; D012999:Soman; D011493:Protein Kinase C; D002802:Cholinesterases