{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T02:04:02Z","timestamp":1791079442916,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2007,10,16]],"date-time":"2007-10-16T00:00:00Z","timestamp":1192492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2008,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cardiomyocyte hypertrophy differs according to the stress exerted on the myocardium. While pressure overload\u2010induced 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\u2010induced physiological and pressure overload\u2010induced pathological hypertrophies. C57BL\/6J mice were either treadmill trained for 6 weeks, 5 days\/week, at 85\u201390% of maximal oxygen uptake (VO<jats:sub>2max<\/jats:sub>), or underwent transverse aortic constriction (TAC) for 1 or 8 weeks. Total and phosphorylated protein levels were determined with SDS\u2010PAGE, and fetal genes by real\u2010time RT\u2010PCR. 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\u20101 (S6K1) and the eukaryotic translation initiation factor\u20104E binding protein\u20101 (4E\u2010BP1). Exercise training did not reactivate the fetal gene program (\u03b2\u2010myosin heavy chain, atrial natriuretic factor, skeletal muscle actin). In contrast, pressure overload after TAC reactivated fetal genes already after 1 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. J. Cell. Physiol. 214: 316\u2013321, 2008. \u00a9 2007 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/jcp.21197","type":"journal-article","created":{"date-parts":[[2007,10,16]],"date-time":"2007-10-16T21:47:03Z","timestamp":1192571223000},"page":"316-321","source":"Crossref","is-referenced-by-count":203,"title":["Activation or inactivation of cardiac Akt\/mTOR signaling diverges physiological from pathological hypertrophy"],"prefix":"10.1002","volume":"214","author":[{"given":"Ole 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