Regulation of cAMP homeostasis by the efflux protein MRP4 in cardiac myocytes

Yassine Sassi, Aniella Abi-Gerges, Jeremy Fauconnier, Nathalie Mougenot, Steven Reiken, Kobra Haghighi, Evangelia G. Kranias, Andrew R. Marks, Alain Lacampagne, Stefan Engelhardt, Stephane N. Hatem, Anne Marie Lompre, Jean Sébastien Hulot

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)1009-1017
Number of pages9
JournalFASEB Journal
Volume26
Issue number3
DOIs
StatePublished - Mar 2012
Externally publishedYes

Keywords

  • Cyclic nucleotides
  • MRP proteins
  • Phosphodiesterases

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