c-Fos mediates angiotensin II-induced aldosterone production and protein synthesis in bovine adrenal glomerulosa cells

Article Article scientifique Article c-Fos mediates angiotensin II-induced aldosterone production and protein synthesis in bovine adrenal glomerulosa cells eng 2008-10-30 2009-03 author Rincon Garriz José Maria Division of Endocrinology, University Hospital, Genève 14, Switzerland. alessandro.capponi@unige.ch 516541 author Suarez Catherine 583610 Département d'anesthésiologie, pharmacologie et soins intensifs (APSIC) Caty Suarez author Capponi Alessandro Mario 24743 1294-1302 10.1210/en.2008-1036 18974265 0013-7227 https://academic.oup.com/endo/article-lookup/doi/10.1210/en.2008-1036 Angiotensin II (AngII), potassium ion, and ACTH are the main factors controlling aldosterone biosynthesis in adrenal glomerulosa cells. AP-1 response elements for the immediate early gene products, c-Fos and c-Jun, have been identified, among others, in the promoter of the steroidogenic acute regulatory (StAR) protein gene, whose expression is acutely regulated by activators of aldosterone production. In bovine glomerulosa cells, AngII treatment led to a rapid and transient increase in c-fos mRNA expression, c-Fos protein expression, and c-Fos phosphorylation. Inhibition of the ERK1/2 MAPK pathway abolished the effect of AngII on c-fos mRNA, protein, and phosphorylation. EMSA and chromatin immunoprecipitation experiments demonstrated that c-Fos binds with c-Jun to the proximal StAR promoter and that AngII treatment increases the amount of c-Fos bound to the promoter. Overexpression of a dominant-negative form of c-Fos with adenoviral vectors inhibited StAR mRNA and StAR protein expression as well as aldosterone biosynthesis in response to AngII. The dominant-negative c-Fos also prevented the increase in protein synthesis induced by AngII in glomerulosa cells, as assessed by [(3)H]leucine incorporation. These results indicate that AngII rapidly induces c-Fos expression and posttranslational modifications. Furthermore, a heterodimeric c-Fos/c-Jun complex binds to the proximal StAR promoter in glomerulosa cells, thus activating StAR gene expression and acute aldosterone biosynthesis. Finally, c-Fos also contributes to other functional responses to the hormone, such as protein synthesis. Aldosterone / metabolism Angiotensin II / pharmacology Animals Cattle Cells, Cultured Female Gene Expression Regulation / drug effects Genes, fos / drug effects Genes, fos / physiology Mitogen-Activated Protein Kinase 1 / metabolism Mitogen-Activated Protein Kinase 3 / metabolism Phosphoproteins / genetics Phosphoproteins / metabolism Phosphorylation Promoter Regions, Genetic Protein Binding Protein Biosynthesis / drug effects Protein Biosynthesis / genetics Proto-Oncogene Proteins c-fos / metabolism Zona Glomerulosa / drug effects Zona Glomerulosa / metabolism Dewey 616 Swiss National Science Foundation Transcriptional control of cholesterol supply and metabolism for adrenal mineralocorticoid biosynthesis 112373 CH Projects 56 Département de médecine 221 false 456 PHYM DEPARTEMENT 786 989 Médecine interne des spécialités (DEMED) Endocrinology 150 3 61f0f9c6-c6f5-4c9c-b703-5cc111c22f67 Article (Published version) Restricted endo1294.pdf 372757 application/pdf 20f524f376ae169fe9475b25f89bb34196ad9a28620c7becbfd72c4414e94758 restrictedAccess Faculté de médecine / Section de médecine clinique / Département de médecine

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Rincon Garriz, José Maria