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Dual role for glucocorticoids in cardiomyocyte hypertrophy and apoptosis.

Authors: Ren, R  Oakley, RH  Cruz-Topete, D  Cidlowski, JA 
Citation: Ren R, etal., Endocrinology. 2012 Nov;153(11):5346-60. doi: 10.1210/en.2012-1563. Epub 2012 Sep 18.
Pubmed: (View Article at PubMed) PMID:22989630
DOI: Full-text: DOI:10.1210/en.2012-1563

Glucocorticoids and their synthetic derivatives are known to alter cardiac function in vivo; however, the nature of these effects and whether glucocorticoids act directly on cardiomyocytes are poorly understood. To explore the role of glucocorticoid signaling in the heart, we used rat embryonic H9C2 cardiomyocytes and primary cardiomyocytes as model systems. Dexamethasone (100 nm) treatment of cardiomyocytes caused a significant increase in cell size and up-regulated the expression of cardiac hypertrophic markers, including atrial natriuretic factor, beta-myosin heavy chain, and skeletal muscle alpha-actin. In contrast, serum deprivation and TNFalpha exposure triggered cardiomyocyte apoptosis, and these apoptotic effects were inhibited by dexamethasone. Both the hypertrophic and anti-apoptotic actions of glucocorticoids were abolished by the glucocorticoid receptor (GR) antagonist RU486 and by short hairpin RNA-mediated GR depletion. Blocking the activity of the mineralocorticoid receptor had no effect on these glucocorticoid-dependent cardiomyocyte responses. Aldosterone (1 mum) activation of GR also promoted cardiomyocyte hypertrophy and cell survival. To elucidate the mechanism of the dual glucocorticoid actions, a genome-wide microarray was performed on H9C2 cardiomyocytes treated with vehicle or dexamethasone in the absence or presence of serum. Serum dramatically influenced the transcriptome regulated by GR, revealing potential glucocorticoid signaling mediators in both cardiomyocyte hypertrophy and apoptosis. These studies reveal a direct and dynamic role for glucocorticoids and GR signaling in the modulation of cardiomyocyte function.

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CRRD Object Information
CRRD ID: 7174736
Created: 2012-11-20
Species: All species
Last Modified: 2012-11-20
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.