Increased AP-1 DNA binding activity in PC12 cells treated with lead

Tamal Chakraborti, Kyung Ah Kim, Gary G. Goldstein, Joseph P. Bressler

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Pages (from-to)187-194
Number of pages8
JournalJournal of Neurochemistry
Volume73
Issue number1
DOIs
StatePublished - 1999

Keywords

  • Activator protein-1 complex
  • Lead
  • PC12 cells
  • Protein kinase C

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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