title: Identification of corticosteroid-regulated genes in cardiomyocytes by serial analysis of gene expression.
abstract: Corticosteroids (aldosterone, cortisol/corticosterone) exert direct functional effects on cardiomyocytes. However, gene networks activated by corticosteroids in cardiomyocytes, as well as the involvement of the mineralocorticoid receptor (MR) vs the glucocorticoid receptor (GR) in these effects, remain largely unknown. Here we characterized the corticosteroid-dependent transcriptome in primary culture of neonatal mouse cardiomyocytes treated with 10(-6) M aldosterone, a concentration predicted to occupy both MR and GR. Serial analysis of gene expression revealed 101 aldosterone-regulated genes. The MR/GR specificity was characterized for one regulated transcript, namely ecto-ADP-ribosyltransferase-3 (Art3). Using cardiomyocytes from GR(null/null) or MR(null/null) mice we demonstrate that in GR(null/null) cardiomyocytes the response is abrogated, but it is fully maintained in MR(null/null) cardiomyocytes. We conclude that Art3 expression is regulated exclusively via the GR. Our study identifies a new set of corticosteroid-regulated genes in cardiomyocytes and demonstrates a new approach to studying the selectivity of MR- vs GR-dependent effects.
authors.affiliation: Cardiology Service, University Hospital, CHUV, CH-1011 Lausanne, Switzerland.
authors.forename: Olivier
authors.initials: O
authors.lastname: Muller
authors.forename: Sylvain
authors.initials: S
authors.lastname: Pradervand
authors.forename: Stefan
authors.initials: S
authors.lastname: Berger
authors.forename: Gabriel
authors.initials: G
authors.lastname: Centeno
authors.forename: Aude
authors.initials: A
authors.lastname: Milet
authors.forename: Pascal
authors.initials: P
authors.lastname: Nicod
authors.forename: Thierry
authors.initials: T
authors.lastname: Pedrazzini
authors.forename: François
authors.initials: F
authors.lastname: Tronche
authors.forename: Günter
authors.initials: G
authors.lastname: Schütz
authors.forename: Kenneth
authors.initials: K
authors.lastname: Chien
authors.forename: Bernard C
authors.initials: BC
authors.lastname: Rossier
authors.forename: Dmitri
authors.initials: D
authors.lastname: Firsov
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D058851:GPI-Linked Proteins; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D058851:GPI-Linked Proteins; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D036002:ADP Ribose Transferases; C448826:Art3 protein, mouse