Abstract |
Both c-Fos and prodynorphin mRNA and peptide increase unilaterally in nociceptive-specific neurons in the lumbar rat spinal cord during chronic hindpaw inflammation. To study the mechanisms underlying prodynorphin gene expression, we examined transcription factors and their interactions at the CRE/AP-1-like site, DYNCRE3, found in the prodynorphin gene promoter. CREB repressed while c-Fos and c-Jun activated transcription through the DYNCRE3 site in transient co-transfections in PC12 cells. Following inflammation of the rat hindpaw, immunostaining demonstrated a bilateral increase in phosphorylated CREB (P-CREB)-positive neurons in the spinal cord. Gel supershift studies showed that spinal cord extracts contained CREB, P-CREB, and phosphorylated c-Jun (P- c-Jun) proteins that bound to the DYNCRE3 site. We propose a model in which inflammation-induced phosphorylation of CREB relieves CREB repression at the DYNCRE3 site, P-CREB binds to the c-Fos promoter, and Fos/Fra, P-CREB, and P-c-Jun interact at the DYNCRE3 site to activate prodynorphin gene transcription.
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Authors | D J Messersmith, D J Kim, M J Iadarola |
Journal | Brain research. Molecular brain research
(Brain Res Mol Brain Res)
Vol. 53
Issue 1-2
Pg. 260-9
(Jan 1998)
ISSN: 0169-328X [Print] Netherlands |
PMID | 9473689
(Publication Type: Journal Article)
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Chemical References |
- Cyclic AMP Response Element-Binding Protein
- Enkephalins
- Protein Precursors
- Proto-Oncogene Proteins c-fos
- Proto-Oncogene Proteins c-jun
- Recombinant Proteins
- Transcription Factor AP-1
- Transcription Factors
- preproenkephalin
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Topics |
- Animals
- Binding Sites
- Cell Nucleus
(metabolism)
- Cyclic AMP Response Element-Binding Protein
(biosynthesis, metabolism)
- Enkephalins
(biosynthesis)
- Gene Expression Regulation
- Hindlimb
- Inflammation
(metabolism)
- Male
- Models, Neurological
- Neurons
(metabolism, physiology)
- PC12 Cells
- Phosphorylation
- Promoter Regions, Genetic
- Protein Precursors
(biosynthesis)
- Proto-Oncogene Proteins c-fos
(metabolism)
- Proto-Oncogene Proteins c-jun
(metabolism)
- Rats
- Rats, Sprague-Dawley
- Recombinant Proteins
(biosynthesis)
- Spinal Cord
(metabolism, physiopathology)
- Transcription Factor AP-1
(metabolism)
- Transcription Factors
(metabolism)
- Transcription, Genetic
- Transfection
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