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Increased AP‐1 DNA Binding Activity in PC12 Cells Treated with Lead
Author(s) -
Chakraborti Tamal,
Kim KyungAh,
Goldstein Gary G.,
Bressler Joseph P.
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0730187.x
Subject(s) - microbiology and biotechnology , electrophoretic mobility shift assay , activator (genetics) , protein kinase a , transfection , kinase , transcription (linguistics) , chemistry , binding protein , dna , protein kinase c , reporter gene , biology , transcription factor , biochemistry , gene , gene expression , linguistics , philosophy
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 Pb 2+ 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 Pb 2+ 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 Pb 2+ 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 Pb 2+ . Fra‐2 and JunD were found in supershift assays to be the major components of the AP‐1 that was increased by Pb 2+ . In summary, our studies indicate that Pb 2+ increases AP‐1 DNA binding activity in PC12 cells by a pathway that requires protein kinase C and new protein synthesis.