AKT2 deficiency induces retardation of myocyte development through EndoG-MEF2A signaling in mouse heart

Biochem Biophys Res Commun. 2017 Dec 2;493(4):1410-1417. doi: 10.1016/j.bbrc.2017.09.149. Epub 2017 Sep 28.


Protein kinase B2 (AKT2) is implicated in diverse process of cardiomyocyte signaling including survival and metabolism. However, the role of AKT2 in myocardium development and the signaling pathway is rarely understood. Therefore, we sought to determine the effect of AKT2 deletion on heart development and its downstream targets. By using experimental animal models and neonatal rat cardiomyocytes (NRCMs), we observed that AKT2 deficiency induces retardation of heart development and increased systemic blood pressure (BP) without affecting cardiac function. Further investigation suggested that deficiency of AKT2 in myocardium results in diminished MEF2A abundance, which induced decreased size of cardiomyocytes. We additionally confirmed that EndoG, which is also regulated by AKT2, is a suppressor of MEF2A in myocardium. Finally, our results proved that AKT2 deficiency impairs the response to β-adrenergic stimuli that normally causes hypertrophy in cardiomyocytes by downregulating MEF2A expression. Our data are the first to show the important role of AKT2 in determining the size of myocardium, its deficiency causes retardation of cardiomyocyte development. We also proved a novel pathway of heart development involving EndoG and MEF2A regulated by AKT2.

Keywords: Endonuclease G (EndoG); Heart; Myocyte enhancer factor 2A (MEF2A); Protein kinase B2 (AKT2).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Size
  • Cells, Cultured
  • Endodeoxyribonucleases / antagonists & inhibitors
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / metabolism*
  • Gene Knockdown Techniques
  • Heart / growth & development
  • MEF2 Transcription Factors / antagonists & inhibitors
  • MEF2 Transcription Factors / genetics
  • MEF2 Transcription Factors / metabolism
  • Mice
  • Mice, Knockout
  • Myocardium / cytology
  • Myocardium / metabolism
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / metabolism*
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / deficiency*
  • Proto-Oncogene Proteins c-akt / genetics
  • RNA, Small Interfering / genetics
  • Rats
  • Signal Transduction


  • MEF2 Transcription Factors
  • MEF2A protein, rat
  • Mef2a protein, mouse
  • RNA, Small Interfering
  • Akt2 protein, mouse
  • Akt2 protein, rat
  • Proto-Oncogene Proteins c-akt
  • Endodeoxyribonucleases
  • endonuclease G