Identification of corticosteroid-regulated genes in cardiomyocytes by serial analysis of gene expression.
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.
Muller
Olivier
O
Cardiology Service, University Hospital, CHUV, CH-1011 Lausanne, Switzerland.
Pradervand
Sylvain
S
Berger
Stefan
S
Centeno
Gabriel
G
Milet
Aude
A
Nicod
Pascal
P
Pedrazzini
Thierry
T
Tronche
François
F
Schütz
Günter
G
Chien
Kenneth
K
Rossier
Bernard C
BC
Firsov
Dmitri
D
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
D058851:GPI-Linked Proteins; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D036002:ADP Ribose Transferases; C448826:Art3 protein, mouse