Increased AP-1 DNA-binding activity and nuclear REF-1 accumulation in lead-exposed primary cultures of astrocytes

• Published in: Neurochemical research 2000-06, Vol.25 (6), p.861-866
• Main Authors: SCORTEGAGNA, M, HANBAUER, I
• Format: Article
• Language: English
• Subjects: Animals; Astrocytes - drug effects; Astrocytes - metabolism; Biological and medical sciences; Carbon-Oxygen Lyases - metabolism; Cell Nucleus - metabolism; Cells, Cultured; Chemical and industrial products toxicology. Toxic occupational diseases; DNA - metabolism; DNA-(Apurinic or Apyrimidinic Site) Lyase; Female; Lead - pharmacology; Medical sciences; Metals and various inorganic compounds; Mice; Mice, Inbred C57BL; redox factor-1; Toxicology; Transcription Factor AP-1 - metabolism
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1023/A:1007577710066

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.