Levels of protein kinase C and nitric oxide synthase activity in rats exposed to sub chronic low level lead.

The intracellular regulation of protein kinase C (PKC) and nitric oxide synthase (NOS) in relation to the accumulation of lead (Pb2+) in various brain regions following low-level lead exposure (50 ppm) for 90 days in rats was investigated. PKC and NOS are important enzymes in mediating cellular transduction mechanisms and in the regulation of neuronal plasticity. Rats exposed to Pb2+ resulted in blood Pb2+ levels similar to those observed in children affected due to Pb2+ exposure. Further, we examined whether Pb2+ accumulation changed the intracellular signaling mechanisms in different brain regions. Results of these experiments indicate that significant region specific Pb2+ accumulation is associated with down regulation of PKC. The down regulation of PKC increased the activity of NOS following Pb2+ exposure. Thus, the change in PKC activity in respect to Pb2+ accumulation increased NOS activity. These results suggest that neuronal toxicity during Pb2+ exposure is linked to the modulation of PKC followed by NOS activation.