title: Increased AP-1 DNA binding activity in PC12 cells treated with lead.
abstract: 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.
authors.affiliation: Department of Neurology, Johns Hopkins University School of Public Health and Hygiene and Kennedy Krieger Research Institute, Baltimore, Maryland 21205, USA.
authors.forename: T
authors.initials: T
authors.lastname: Chakraborti
authors.forename: K A
authors.initials: KA
authors.lastname: Kim
authors.forename: G G
authors.initials: GG
authors.lastname: Goldstein
authors.forename: J P
authors.initials: JP
authors.lastname: Bressler
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D016762:Genes, fos; D016758:Genes, jun; D007700:Kinetics; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000494:pharmacology*; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D009942:Organometallic Compounds; D011500:Protein Synthesis Inhibitors; D018808:Transcription Factor AP-1; D015240:Phorbol 12,13-Dibutyrate; D004247:DNA; D011493:Protein Kinase C; C008261:lead acetate