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 inte racting with protein thiol groups or indirectly by mimicking Ca2+ and incre asing oxidative stress. In view of the potential action of Pb on cellular r edox homeostasis we studied the regulation of activator protein-1 (AP-1) DN A binding. A 1h incubation of astrocyte primary cultures with 10 mu M Pb ca used a 2.5 fold increase in AP-1 DNA binding. An assessment of how Pb elici ted this increase revealed the involvement of 1. transcriptional and 2. pos ttranslational processes. The first one was documented by an increase of c- jun mRNA content after 15 to 30 min of 10 mu M Pb exposure. The second one was suggested by an enhanced nuclear accumulation of redox factor-1 after 3 0 to 60 min of 10 mu M Pb exposure. The Pb-elicited increase of the reducti on/oxidation-sensitive AP-1 signal transduction may regulate target genes o perative in cell survival or cell death.