Transcription factor regulation of prodynorphin gene expression following rat hindpaw inflammation

• Published in: Brain research. Molecular brain research. Vol. 53; no. 1; pp. 259 - 269
• Main Authors: Messersmith, Donna J, Kim, David J, Iadarola, Michael J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 1998; Elsevier
• Subjects: Biological and medical sciences; c-Jun; CREB phosphorylation; Cyclic AMP response element binding protein; Dynorphin; Fos; Fra; Fundamental and applied biological sciences. Psychology; Inflammation; Molecular and cellular biology; Nociception; Nociception; c-Jun; Fra; Cyclic AMP response element binding protein; Dynorphin; CREB phosphorylation; Fos; Vertebrata; Hindlimb; Regulation(control); Mammalia; Prodynorphin; Rat; Rodentia; Inflammation; Gene expression; Transcription factor; Transcription factor CREB
• ISSN: 0169-328X; 1872-6941
• DOI: 10.1016/S0169-328X(97)00308-2

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.