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

Tamal Chakraborti, Kyung Ah Kim, Gary William Goldstein, Joseph Bressler

Research output: Contribution to journalArticle

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

Fingerprint

PC12 Cells
Transcription Factor AP-1
Protein Kinase C
DNA
Transcription
Assays
Electrophoretic mobility
Protein C Inhibitor
Electrophoretic Mobility Shift Assay
Protein Kinase Inhibitors
Luciferases
Reporter Genes
Lead
Proteins
Genes
Gels

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Increased AP-1 DNA binding activity in PC12 cells treated with lead. / Chakraborti, Tamal; Kim, Kyung Ah; Goldstein, Gary William; Bressler, Joseph.

In: Journal of Neurochemistry, Vol. 73, No. 1, 1999, p. 187-194.

Research output: Contribution to journalArticle

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