RESUMEN
The possibility that the mechanism of lead neurotoxicity may be at the level of transcription was investigated in PC12 cells. In electrophoretic mobility gel shift assays Pb2+ was found to increase activator protein-1 complex (AP-1) DNA binding activity in PC12 cells; the increase was time- and concentration-dependent. Exposure to Pb2+ also resulted in an increase in AP-1-driven transcription in cerebellar granule cells transfected with a luciferase gene reporter construct. The increase in AP-1 DNA binding activity by Pb2+ required protein synthesis. The increase was mediated by protein kinase C because depletion of protein kinase C and an inhibitor of protein kinase C prevented the increase in AP-1 DNA binding activity by Pb2+. Fra-2 and JunD were found in supershift assays to be the major components of the AP-1 that was increased by Pb2+. In summary, our studies indicate that Pb2+ increases AP-1 DNA binding activity in PC12 cells by a pathway that requires protein kinase C and new protein synthesis.