Increased AP-1 DNA-binding activity and nuclear REF-1 accumulation in lead-exposed primary cultures of astrocytes.

Pb was shown to perturb neuronal and glial function either directly by interacting with protein thiol groups or indirectly by mimicking Ca(2+) and increasing oxidative stress. In view of the potential action of Pb on cellular redox homeostasis we studied the regulation of activator protein-1 (AP-1) DNA binding. A 1h incubation of astrocyte primary cultures with 10 microM Pb caused a 2.5 fold increase in AP-1 DNA binding. An assessment of how Pb elicited this increase revealed the involvement of 1. transcriptional and 2. posttranslational processes. The first one was documented by an increase of c-jun mRNA content after 15 to 30 min of 10 microM Pb exposure. The second one was suggested by an enhanced nuclear accumulation of redox factor-1 after 30 to 60 min of 10 microM Pb exposure. The Pb-elicited increase of the reduction/oxidation-sensitive AP-1 signal transduction may regulate target genes operative in cell survival or cell death.