title: Immediate-early transcriptional response to angiotensin II in human adrenocortical cells.
abstract: Angiotensin II binds to the angiotensin II receptors type 1 (AT1 receptors) in adrenocortical cells and triggers an intracellular signaling cascade leading to changes in the gene expression pattern. Here, we show that stimulation with angiotensin II induces the expression of biologically active early growth response (Egr)-1, a zinc finger transcription factor, in human H295R adrenocortical cells. Expression of a dominant-negative mutant of the ternary complex factor Elk-1, a key transcriptional regulator of serum response element-driven gene transcription, prevented Egr-1 expression in angiotensin II-stimulated H295R cells, indicating that Ets-like protein-1 (Elk-1) or related ternary complex factors connect the intracellular signaling cascade elicited by activation of AT1 receptors with transcription of the Egr-1 gene. These data were corroborated by the fact that angiotensin II stimulation increased the transcription activation potential of Elk-1. In addition, activator protein-1 transcriptional activity was significantly elevated in angiotensin II-treated H295R cells. Expression of c-Jun and c-Fos was increased as well as the transcription activation potential of c-Fos. Expression of a dominant-negative mutant of Elk-1 reduced c-Fos expression in angiotensin II-stimulated adrenocortical cells, suggesting that the serum response element within the c-Fos promoter functions as an angiotensin II-response element. Expression of a dominant-negative mutant of c-Jun reduced activator protein-1 activity in angiotensin II-stimulated adrenocortical cells and reduced the up-regulation of c-Jun after angiotensin II stimulation. Thus, c-Jun regulates its own expression in adrenocortical cells. Together, the data show that angiotensin II stimulation activates the transcription factors Egr-1, Elk-1, c-Jun, and c-Fos in adrenocortical cells, leading to stimulus-dependent changes in the gene expression pattern.
authors.affiliation: Department of Medical Biochemistry and Molecular Biology, Building 44, University of Saarland Medical Center, D-66421 Homburg, Germany. gerald.thiel@uks.eu
authors.forename: Gerald
authors.initials: G
authors.lastname: Thiel
authors.forename: Oliver G
authors.initials: OG
authors.lastname: Rössler
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D002460:Cell Line; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D011401:Promoter Regions, Genetic / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects*; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects; D050807:ets-Domain Protein Elk-1 / Q000235:genetics / Q000378:metabolism
chemical_list: C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D044140:Receptor, Angiotensin, Type 1; D018808:Transcription Factor AP-1; D050807:ets-Domain Protein Elk-1; D000804:Angiotensin II