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.

journal_name

J Neurochem

authors

Chakraborti T,Kim KA,Goldstein GG,Bressler JP

doi

10.1046/j.1471-4159.1999.0730187.x

keywords:

subject

Has Abstract

pub_date

1999-07-01 00:00:00

pages

187-94

issue

1

eissn

0022-3042

issn

1471-4159

journal_volume

73

pub_type

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