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.
Original language | English (US) |
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Pages (from-to) | 187-194 |
Number of pages | 8 |
Journal | Journal of Neurochemistry |
Volume | 73 |
Issue number | 1 |
DOIs | |
State | Published - 1999 |
Keywords
- Activator protein-1 complex
- Lead
- PC12 cells
- Protein kinase C
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience