Synergistic induction of neurotensin gene transcription in PC12 cells parallels changes in AP-1 activity
Biochemistry & Molecular Pharmacology
Graduate School of Biomedical Sciences; Department of Molecular Genetics and Microbiology
Medical Subject Headings
Animals; Base Sequence; Cyclic AMP; Cycloheximide; Forskolin; Gene Expression; Lithium; Molecular Sequence Data; Nerve Growth Factors; Neuropeptides; Neurotensin; PC12 Cells; Rats; Transcription Factor AP-1
Life Sciences | Medicine and Health Sciences
A consensus AP-1 site in the promoter of the rat neurotensin/neuromedin N (NT/N) gene is a critical regulatory element required for synergistic regulation by combinations of nerve growth factor (NGF), lithium, glucocorticoids, and adenylate cyclase activators. A rapid RNase protection assay was developed to examine the kinetics of NT/N gene activation and to determine whether activation requires newly synthesized proteins. Either NGF or lithium in combination with dexamethasone and forskolin transiently activated NT/N gene expression, but with distinct kinetics. Protein synthesis was not required for activation when NGF was used as the permissive inducer, but was required for the rapid down-regulation of the response. In contrast, lithium responses were attenuated in the absence of protein synthesis, consistent with a requirement for newly synthesized AP-1 complexes in activation. In all cases, increases in NT/N gene expression closely paralleled increases in AP-1 binding activity. Lithium in combination with other inducers caused delayed increases in both AP-1 binding activity and c-jun, c-fos and fra-1 gene expression. These results indicate that NGF and lithium exert their effects on NT/N gene expression through distinct pathways. The lithium pathway is active in neuronally-differentiated PC12 cells and could potentially be involved in the regulation of NT/N gene expression in the nervous system.
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Citation: Brain Res Mol Brain Res. 1994 Dec;27(2):232-42.
Brain research. Molecular brain research
Bullock, Bryant Paul; McNeil, Gerard P.; and Dobner, Paul R., "Synergistic induction of neurotensin gene transcription in PC12 cells parallels changes in AP-1 activity" (1994). GSBS Student Publications. 152.