Activation or inactivation of cardiac Akt/mTOR signaling diverges physiological from pathological hypertrophy

Ole Johan Kemi, Marcello Ceci, Ulrik Wisloff, Serena Grimaldi, Paolo Gallo, Godfrey L. Smith, Gianluigi Condorelli, Oyvind Ellingsen

Research output: Contribution to journalArticle

138 Citations (Scopus)

Abstract

Cardiomyocyte hypertrophy differs according to the stress exerted on the myocardium. While pressure overload-induced cardiomyocyte hypertrophy is associated with depressed contractile function, physiological hypertrophy after exercise training associates with preserved or increased inotropy. We determined the activation state of myocardial Akt signaling with downstream substrates and fetal gene reactivation in exercise-induced physiological and pressure overload-induced pathological hypertrophies. C57BL/6J mice were either treadmill trained for 6 weeks, 5 days/week, at 85-90% of maximal oxygen uptake (VO 2max), or underwent transverse aortic constriction (TAC) for 1 or 8 weeks. Total and phosphorylated protein levels were determined with SDS-PAGE, and fetal genes by real-time RT-PCR. In the physiologically hypertrophied heart after exercise training, total Akt protein level was unchanged, but Akt was chronically hyperphosphorylated at serine 473. This was accompanied by activation of the mammalian target of rapamycin (mTOR), measured as phosphorylation of its two substrates: the ribosomal protein S6 kinase-I (S6KI) and the eukaryotic translation initiation factor-4E binding protein-I (4E-BPI ). Exercise training did not reactivate the fetal gene program (β-myosin heavy chain, atrial natriuretic factor, skeletal muscle actin). In contrast, pressure overload after TAC reactivated fetal genes already after I week, and partially inactivated the Akt/mTOR pathway and downstream substrates after 8 weeks. In conclusion, changes in opposite directions of the myocardial Akt/mTOR signal pathway appears to distinguish between physiological and pathological hypertrophies; exercise training associating with activation and pressure overload associating with inactivation of the Akt/mTOR pathway.

Original languageEnglish
Pages (from-to)316-321
Number of pages6
JournalJournal of Cellular Physiology
Volume214
Issue number2
DOIs
Publication statusPublished - Feb 2008

Fingerprint

Sirolimus
Hypertrophy
Genes
Chemical activation
Exercise
Pressure
Substrates
Cardiac Myocytes
Constriction
Ribosomal Protein S6 Kinases
Eukaryotic Initiation Factors
Exercise equipment
Phosphorylation
Eukaryotic Initiation Factor-4E
Myosin Heavy Chains
Atrial Natriuretic Factor
Serine
Muscle
Actins
Carrier Proteins

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Kemi, O. J., Ceci, M., Wisloff, U., Grimaldi, S., Gallo, P., Smith, G. L., ... Ellingsen, O. (2008). Activation or inactivation of cardiac Akt/mTOR signaling diverges physiological from pathological hypertrophy. Journal of Cellular Physiology, 214(2), 316-321. https://doi.org/10.1002/jcp.21197

Activation or inactivation of cardiac Akt/mTOR signaling diverges physiological from pathological hypertrophy. / Kemi, Ole Johan; Ceci, Marcello; Wisloff, Ulrik; Grimaldi, Serena; Gallo, Paolo; Smith, Godfrey L.; Condorelli, Gianluigi; Ellingsen, Oyvind.

In: Journal of Cellular Physiology, Vol. 214, No. 2, 02.2008, p. 316-321.

Research output: Contribution to journalArticle

Kemi, Ole Johan ; Ceci, Marcello ; Wisloff, Ulrik ; Grimaldi, Serena ; Gallo, Paolo ; Smith, Godfrey L. ; Condorelli, Gianluigi ; Ellingsen, Oyvind. / Activation or inactivation of cardiac Akt/mTOR signaling diverges physiological from pathological hypertrophy. In: Journal of Cellular Physiology. 2008 ; Vol. 214, No. 2. pp. 316-321.
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