Lead-induced developmental changes in AP-1 DNA binding in rat brain

Keith R. Pennypacker, Yang Xiao, Ruo H. Xu, G. Jean Harry

Research output: Contribution to journalArticlepeer-review

20 Scopus citations


Exposure to lead during ontogeny is detrimental to the growth and development of the brain. Morphological abnormalities occur in the developing brain, which are manifested as mental retardation and other neurological disorders. Despite extensive research, the biochemical mechanism for neurological effects of lead has not been established but appears to be at the level of the genome since aberrant expression of developmentally-important genes has been reported. Basal levels of activator protein 1 (AP-1) transcription factor DNA binding are elevated in the rat brain during the early postnatal period. The AP-1 DNA binding complex is composed of a Jun:cAMP responsive element binding protein dimer, which appears to modulate expression of developmentally-important genes that contain AP-1 binding sites in their promoter. Brain regions from perinatally lead-exposed rats were examined on postnatal days 3, 9 and 15 for DNA binding activity to the AP-1 DNA sequence. AP-1 DNA binding activities were significantly increased on postnatal day 3 in hippocampus and cortex from lead-treated rats with no other area (frontal lobe or brainstem) or timepoint showing significant changes. Since no increases were detected in the level of Jun protein which is a component of the AP-1 binding complex, post-translational modification may be involved in enhancing DNA binding activity. By altering levels of AP-1 DNA binding to the promoter regions, lead exposure may be changing the levels of mRNA synthesis of developmentally important genes.

Original languageEnglish
Pages (from-to)321-328
Number of pages8
JournalInternational Journal of Developmental Neuroscience
Issue number3
StatePublished - Jun 5 1997


  • Jun
  • Neurotoxicity
  • Transcription factor

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Developmental Biology


Dive into the research topics of 'Lead-induced developmental changes in AP-1 DNA binding in rat brain'. Together they form a unique fingerprint.

Cite this