Journal
FASEB JOURNAL
Volume 26, Issue 3, Pages 1009-1017Publisher
WILEY
DOI: 10.1096/fj.11-194027
Keywords
cyclic nucleotides; MRP proteins; phosphodiesterases
Categories
Funding
- Agence Nationale de la Recherche (ANR) [09JCJC0112]
- Fondation de France [2006005606]
- Fondation Leducq through CAERUS network [05CVD03]
- U.S. National Institutes of Health [NIH HL26057, HL64018]
- French Ministere de l'Education Nationale et de la Recherche Scientifique (MENRS)
- Fondation pour la Recherche Medicale (FRM)
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Recent studies indicate that members of the multidrug-resistance protein (MRP) family belonging to ATP binding cassette type C (ABCC) membrane proteins extrude cyclic nucleotides from various cell types. This study aimed to determine whether MRP proteins regulate cardiac cAMP homeostasis. Here, we demonstrate that MRP4 is the predominant isoform present at the plasma membrane of cardiacmyocytes and that it mediates the efflux of cAMP in these cells. MRP4-deficient mice displayed enhanced cardiac myocyte cAMP formation, contractility, and cardiac hypertrophy at 9 mo of age, an effect that was compensated transiently by increased phosphodiesterase expression at young age. These findings suggest that cAMP extrusion via MRP4 acts together with phosphodiesterases to control cAMP levels in cardiac myocytes.-Sassi, Y., Abi-Gerges, A., Fauconnier, J., Mougenot, N., Reiken, S., Haghighi, K., Kranias, E. G., Marks, A. R., Lacampagne, A., Engelhardt, S., Hatem, S. N., Lompre, A.-M., Hulot, J. S. Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes. FASEB J. 26, 1009-1017 (2012). www.fasebj.org
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