Effect of Soman on Protein Phosphorylation in Brain

摘要

The purpose of this project is to determine some of the cholinergic-dependent as well as possible cholinergic-independent effects of soman on protein phosphorylating systems in brain. An understanding of the effects of soman treatment on the activity of protein kinases and the subsequent phosphorylation of substrate protein will enable the development of new approaches to the treatment of soman toxicity. Studies were conducted to determine the effects of treatment with soman on calcium/calmodulin and calcium/phospholipid-dependent protein kinase and protein phosphatase activity in selected regions of rat brain. With the exception of calcium/phospholipid-dependent protein kinase activity in the soluble fraction of the neo-cortex and cerebellum, no significant differences were noted between soman and saline treatment with regard to calcium-dependent protein kinase and phosphate activity. Studies were also conducted to identify brain proteins phosphorylated by cholinergic-dependent mechanisms. Several such proteins were identified; the most prominent of these is a substrate for the calcium/phospholipid-dependent protein kinase. The results indicate that treatment with soman can activate both calcium/calmodulin-dependent and calcium/phospholipid-dependent protein kinase in brain. (kt)