Increased AP-1 DNA-binding activity and nuclear REF-1 accumulation in lead-exposed primary cultures of astrocytes.
Pb was shown to perturb neuronal and glial function either directly by interacting with protein thiol groups or indirectly by mimicking Ca(2+) and increasing oxidative stress. In view of the potential action of Pb on cellular redox homeostasis we studied the regulation of activator protein-1 (AP-1) DNA binding. A 1h incubation of astrocyte primary cultures with 10 microM Pb caused a 2.5 fold increase in AP-1 DNA binding. An assessment of how Pb elicited this increase revealed the involvement of 1. transcriptional and 2. posttranslational processes. The first one was documented by an increase of c-jun mRNA content after 15 to 30 min of 10 microM Pb exposure. The second one was suggested by an enhanced nuclear accumulation of redox factor-1 after 30 to 60 min of 10 microM Pb exposure. The Pb-elicited increase of the reduction/oxidation-sensitive AP-1 signal transduction may regulate target genes operative in cell survival or cell death.
Scortegagna
M
M
Laboratory of Molecular Immunology, NHLBI, NIH, Bethesda, MD 20892-1674, USA.
Hanbauer
I
I
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D019757:Carbon-Oxygen Lyases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D005260:Female; D007854:Lead / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D018808:Transcription Factor AP-1; D007854:Lead; D004247:DNA; D019757:Carbon-Oxygen Lyases; C486216:Apex1 protein, mouse; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase