AMPKalpha2 counteracts the development of cardiac hypertrophy induced by isoproterenol.
As AMP-activated protein kinase (AMPK) controls protein translation, an anti-hypertrophic effect of AMPK has been suggested. However, there is no genetic evidence to confirm this hypothesis. We investigated the contribution of AMPKalpha2 in the control of cardiac hypertrophy by using AMPKalpha2-/- mice submitted to isoproterenol. The isoproterenol-induced cardiac hypertrophy, measured by left ventricular mass and histological examination, was significantly higher in AMPKalpha2-/- than in WT animals. Moreover, the intensification of cardiac hypertrophy found in AMPKalpha2-/- mice can be linked to the abnormal basal overstimulation of the p70 ribosomal S6 protein kinase, an enzyme known to regulate protein translation and cell growth. In conclusion, this work shows that AMPKalpha2 plays a role of brake for the development of cardiac hypertrophy.
Zarrinpashneh
Elham
E
Université catholique de Louvain, Division of Cardiology, 55 Avenue Hippocrate, CARD5550, B-1200 Brussels, Belgium.
Beauloye
Christophe
C
Ginion
Audrey
A
Pouleur
Anne-Catherine
AC
Havaux
Xavier
X
Hue
Louis
L
Viollet
Benoit
B
Vanoverschelde
Jean-Louis
JL
Bertrand
Luc
L
D055372:AMP-Activated Protein Kinases; D000818:Animals; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D007545:Isoproterenol / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000378:metabolism
D009097:Multienzyme Complexes; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D055372:AMP-Activated Protein Kinases; D007545:Isoproterenol