Neuronal excitation-driven and AP-1-dependent activation of tissue inhibitor of metalloproteinases-1 gene expression in rodent hippocampus

J Biol Chem. 1999 Oct 1;274(40):28106-12. doi: 10.1074/jbc.274.40.28106.

Abstract

Understanding of biological function of AP-1 transcription factor in central nervous system may greatly benefit from identifying its target genes. In this study, we present several lines of evidence implying AP-1 in regulating expression of tissue inhibitor of metalloproteinases-1 (timp-1) gene in rodent hippocampus in response to increased neuronal excitation. Such a notion is supported by the findings that timp-1 mRNA accumulation occurs in the rat hippocampus after either kainate- or pentylenetetrazole-evoked seizures with a delayed, in comparison with AP-1 components, time course, as well as with spatial overlap with c-Fos protein (major inducible AP-1 component) expression. Furthermore, AP-1 sequence derived from timp-1 promoter is specifically bound by hippocampal AP-1 proteins after treating the rats with either pro-convulsive agent. Finally, timp-1 promoter responds to excitatory activation both in vivo, in transgenic mice harboring the timp-LacZ gene construct, and in vitro in neurons of the hippocampal dentate gyrus cultures. These findings suggest that the AP-1 transcription factor may exert its role in the brain through affecting extracellular matrix remodeling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dentate Gyrus / cytology
  • Dentate Gyrus / metabolism*
  • Gene Expression Regulation / physiology*
  • Lac Operon
  • Male
  • Mice
  • Mice, Transgenic
  • Neurons / physiology*
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Wistar
  • Regulatory Sequences, Nucleic Acid
  • Tissue Inhibitor of Metalloproteinase-1 / genetics*
  • Transcription Factor AP-1 / metabolism
  • Transcription Factor AP-1 / physiology*

Substances

  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Transcription Factor AP-1