Glucocorticoid activation of the neuronal nicotinic acetylcholine receptor alpha7 subunit gene: involvement of transcription factor Egr-1.
The alpha7 subunit is a component of nicotinic acetylcholine receptors expressed in bovine chromaffin cells. The peculiar localization of these receptors at adrenomedullary areas adjacent to the adrenal cortex suggests that factors, probably glucocorticoids, arising from the cortex might diffuse and regulate alpha7 receptor expression. In reporter gene transfection experiments, dexamethasone increased alpha7 promoter activity by up to fivefold in a concentration- and time-dependent manner despite the absence of consensus glucocorticoid receptor elements at the alpha7 promoter. Transcriptional activation induced by glucocorticoids was abolished through simultaneous mutation of at least two of the three sites for the immediate early transcription factor Egr-1, present in the proximal promoter region of the alpha7 subunit gene. Therefore, glucocorticoids activate the alpha7 subunit gene through Egr-1 in an indirect way.
Carrasco-Serrano
Carmen
C
Department of Biochemistry and Molecular Biology and Instituto de Neurociencias, Universidad Miguel Hernández-C.S.I.C., 03550-San Juan, Alicante, Spain.
Criado
Manuel
M
D000818:Animals; D001483:Base Sequence; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003907:Dexamethasone / Q000494:pharmacology; D017930:Genes, Reporter; D005938:Glucocorticoids / Q000494:pharmacology*; D008156:Luciferases / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D021122:Protein Subunits; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D064569:alpha7 Nicotinic Acetylcholine Receptor
D005938:Glucocorticoids; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor; D003907:Dexamethasone; D008156:Luciferases