Neuronal excitation-driven and AP-1-dependent activation of tissue inhibitor of metalloproteinases-1 gene expression in rodent hippocampus.
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.
Jaworski
J
J
Nencki Institute, Laboratory of Molecular Neurobiology, Pasteura 3, 02-093 Warsaw, Poland.
Biedermann
I W
IW
Lapinska
J
J
Szklarczyk
A
A
Figiel
I
I
Konopka
D
D
Nowicka
D
D
Filipkowski
R K
RK
Hetman
M
M
Kowalczyk
A
A
Kaczmarek
L
L
D000818:Animals; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D007763:Lac Operon; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012045:Regulatory Sequences, Nucleic Acid; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D018808:Transcription Factor AP-1 / Q000378:metabolism / Q000502:physiology*
D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D018808:Transcription Factor AP-1