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Chronic akt activation accentuates aging-induced cardiac hypertrophy and myocardial contractile dysfunction: role of autophagy

Hua, Yinan, Zhang, Yingmei, Ceylan-Isik, Asli F., Wold, Loren E., Nunn, Jennifer M., Ren, Jun·2011·Basic Research in Cardiology
DOI 10.1007/s00395-011-0222-8
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Abstract

Aging is often accompanied with geometric and functional changes in the heart, although the underlying mechanisms remain unclear. Recent evidence has described a potential role of Akt and autophagy in aging-associated organ deterioration. This study was to examine the impact of cardiac-specific Akt activation on aging-induced cardiac geometric and functional changes and underlying mechanisms involved. Cardiac geometry, contractile and intracellular Ca(2+) properties were evaluated using echocardiography, edge-detection and fura-2 techniques. Level of insulin signaling and autophagy was evaluated by western blot. Our results revealed cardiac hypertrophy (enlarged chamber size, wall thickness, myocyte cross-sectional area), fibrosis, decreased cardiac contractility, prolonged relengthening along with compromised intracellular Ca(2+) release and clearance in aged (24-26 month-old) mice compared with young (3-4 month-old) mice, the effects of which were accentuated by chronic Akt activation. Aging enhanced Akt and mTOR phosphorylation while reducing that of PTEN, AMPK and ACC with a more pronounced response in Akt transgenic mice. GSK3β phosphorylation and eNOS levels were unaffected by aging or Akt overexpression. Levels of beclin-1, Atg5 and LC3-II-to-LC3-I ratio were decreased in aged hearts, the effect of which with the exception of Atg 5 was exacerbated by Akt overactivation. Levels of p62 were significantly enhanced in aged mice with a more pronounced increase in Akt mice.…

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Research works printed but not linked: 60

  1. Alvers AL, Fishwick LK, Wood MS, Hu D, Chung HS, Dunn WA Jr, Aris JP (2009) Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae. Aging Cell 8:353–369. doi: 10.1111/j.1474-9726.2009.00469.x · DOI
  2. Baudhuin P (1966) Lysosomes and cellular autophagy. Brux Med 46:1059–1070
  3. Birnbaum Y, Long B, Qian J, Perez-Polo JR, Ye Y (2011) Pioglitazone limits myocardial infarct size, activates Akt, and upregulates cPLA2 and COX-2 in a PPAR-gamma-independent manner. Basic Res Cardiol 106:431–446. doi: 10.1007/s00395-011-0162-3 · DOI
  4. Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L (2010) Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab 11:35–46. doi: 10.1016/j.cmet.2009.11.010 · DOI · Paper page
  5. Blagosklonny MV (2008) Aging: ROS or TOR. Cell Cycle 7:3344–3354. doi: 10.4161/cc.7.21.6965 · DOI · Paper page
  6. Boengler K, Buechert A, Heinen Y, Roeskes C, Hilfiker-Kleiner D, Heusch G, Schulz R (2008) Cardioprotection by ischemic postconditioning is lost in aged and STAT3-deficient mice. Circ Res 102:131–135. doi: 10.1161/CIRCRESAHA.107.164699 · DOI
  7. Boengler K, Konietzka I, Buechert A, Heinen Y, Garcia-Dorado D, Heusch G, Schulz R (2007) Loss of ischemic preconditioning’s cardioprotection in aged mouse hearts is associated with reduced gap junctional and mitochondrial levels of connexin 43. Am J Physiol Heart Circ Physiol 292:H1764–H1769. doi: 10.1152/ajpheart.01071.2006 · DOI
  8. Boengler K, Schulz R, Heusch G (2009) Loss of cardioprotection with ageing. Cardiovasc Res 83:247–261. doi: 10.1093/cvr/cvp033 · DOI
  9. Breivik L, Helgeland E, Aarnes EK, Mrdalj J, Jonassen AK (2011) Remote postconditioning by humoral factors in effluent from ischemic preconditioned rat hearts is mediated via PI3K/Akt-dependent cell-survival signaling at reperfusion. Basic Res Cardiol 106:135–145. doi: 10.1007/s00395-010-0133-0 · DOI
  10. Carneiro-Ramos MS, Diniz GP, Nadu AP, Almeida J, Vieira RL, Santos RA, Barreto-Chaves ML (2010) Blockage of angiotensin II type 2 receptor prevents thyroxine-mediated cardiac hypertrophy by blocking Akt activation. Basic Res Cardiol 105:325–335. doi: 10.1007/s00395-010-0089-0 · DOI
  11. Ceylan-Isik AF, Zhao P, Zhang B, Xiao X, Su G, Ren J (2010) Cardiac overexpression of metallothionein rescues cardiac contractile dysfunction and endoplasmic reticulum stress but not autophagy in sepsis. J Mol Cell Cardiol 48:367–378. doi: 10.1016/j.yjmcc.2009.11.003 · DOI
  12. Davidoff AJ, Mason MM, Davidson MB, Carmody MW, Hintz KK, Wold LE, Podolin DA, Ren J (2004) Sucrose-induced cardiomyocyte dysfunction is both preventable and reversible with clinically relevant treatments. Am J Physiol Endocrinol Metab 286:E718–E724. doi: 10.1152/ajpendo.00358.2003 · DOI
  13. De Meyer GR, De Keulenaer GW, Martinet W (2010) Role of autophagy in heart failure associated with aging. Heart Fail Rev 15:423–430. doi: 10.1007/s10741-010-9166-6 · DOI
  14. Diniz GP, Carneiro-Ramos MS, Barreto-Chaves ML (2009) Angiotensin type 1 receptor mediates thyroid hormone-induced cardiomyocyte hypertrophy through the Akt/GSK-3beta/mTOR signaling pathway. Basic Res Cardiol 104:653–667. doi: 10.1007/s00395-009-0043-1 · DOI
  15. Doser TA, Turdi S, Thomas DP, Epstein PN, Li SY, Ren J (2009) Transgenic overexpression of aldehyde dehydrogenase-2 rescues chronic alcohol intake-induced myocardial hypertrophy and contractile dysfunction. Circulation 119:1941–1949. doi: 10.1161/CIRCULATIONAHA.108.823799 · DOI
  16. Eskelinen EL (2006) Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Mol Aspects Med 27:495–502. doi: 10.1016/j.mam.2006.08.005 · DOI
  17. Fujita K, Maeda D, Xiao Q, Srinivasula SM (2011) Nrf2-mediated induction of p62 controls Toll-like receptor-4-driven aggresome-like induced structure formation and autophagic degradation. Proc Natl Acad Sci USA 108:1427–1432. doi: 10.1073/pnas.1014156108 · DOI
  18. Ghaboura N, Tamareille S, Ducluzeau PH, Grimaud L, Loufrani L, Croue A, Tourmen Y, Henrion D, Furber A, Prunier F (2011) Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3beta signaling. Basic Res Cardiol 106:147–162. doi: 10.1007/s00395-010-0130-3 · DOI
  19. Goswami SK, Das DK (2006) Autophagy in the myocardium: dying for survival? Exp Clin Cardiol 11:183–188
  20. Gottlieb RA, Finley KD, Mentzer RM Jr (2009) Cardioprotection requires taking out the trash. Basic Res Cardiol 104:169–180. doi: 10.1007/s00395-009-0011-9 · DOI
  21. Ha SD, Ham B, Mogridge J, Saftig P, Lin S, Kim SO (2010) Cathepsin B-mediated autophagy flux facilitates the anthrax toxin receptor 2-mediated delivery of anthrax lethal factor into the cytoplasm. J Biol Chem 285:2120–2129. doi: 10.1074/jbc.M109.065813 · DOI
  22. Hamacher-Brady A, Brady NR, Gottlieb RA (2006) Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac myocytes. J Biol Chem 281:29776–29787. doi: 10.1074/jbc.M603783200 · DOI · Paper page
  23. Hands SL, Proud CG, Wyttenbach A (2009) mTOR’s role in ageing: protein synthesis or autophagy? Aging (Albany NY) 1:586–597 · DOI
  24. Hars ES, Qi H, Ryazanov AG, Jin S, Cai L, Hu C, Liu LF (2007) Autophagy regulates ageing in C. elegans. Autophagy 3:93–95 · DOI · Paper page
  25. Hay N, Sonenberg N (2004) Upstream and downstream of mTOR. Genes Dev 18:1926–1945. doi: 10.1101/gad.1212704 · DOI · Paper page
  26. Iida RH, Kanko S, Suga T, Morito M, Yamane A (2011) Autophagic-lysosomal pathway functions in the masseter and tongue muscles in the klotho mouse, a mouse model for aging. Mol Cell Biochem 348:89–98. doi: 10.1007/s11010-010-0642-z · DOI
  27. Inuzuka Y, Okuda J, Kawashima T, Kato T, Niizuma S, Tamaki Y, Iwanaga Y, Yoshida Y, Kosugi R, Watanabe-Maeda K, Machida Y, Tsuji S, Aburatani H, Izumi T, Kita T, Shioi T (2009) Suppression of phosphoinositide 3-kinase prevents cardiac aging in mice. Circulation 120:1695–1703. doi: 10.1161/CIRCULATIONAHA.109.871137 · DOI
  28. Johansen T, Lamark T (2011) Selective autophagy mediated by autophagic adapter proteins. Autophagy 7:279–296. doi: 10.4161/auto.7.3.14487 · DOI
  29. Kanaan NM, Kordower JH, Collier TJ (2007) Age-related accumulation of Marinesco bodies and lipofuscin in rhesus monkey midbrain dopamine neurons: relevance to selective neuronal vulnerability. J Comp Neurol 502:683–700. doi: 10.1002/cne.21333 · DOI
  30. Koldovsky O (1971) Developmental changes of beta-galactosidase and beta-glucuronidase in the rat liver and kidney. Arch Biochem Biophys 142:378–381 · DOI
  31. Kovacic S, Soltys CL, Barr AJ, Shiojima I, Walsh K, Dyck JR (2003) Akt activity negatively regulates phosphorylation of AMP-activated protein kinase in the heart. J Biol Chem 278:39422–39427. doi: 10.1074/jbc.M305371200 · DOI
  32. Kudo N, Barr AJ, Barr RL, Desai S, Lopaschuk GD (1995) High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5′-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J Biol Chem 270:17513–17520 · DOI
  33. Lakatta EG (1999) Cardiovascular aging research: the next horizons. J Am Geriatr Soc 47:613–625 · DOI
  34. Li Q, Ceylan-Isik AF, Li J, Ren J (2008) Deficiency of insulin-like growth factor 1 reduces sensitivity to aging-associated cardiomyocyte dysfunction. Rejuvenation Res 11:725–733. doi: 10.1089/rej.2008.0717 · DOI
  35. Li Q, Ren J (2007) Influence of cardiac-specific overexpression of insulin-like growth factor 1 on lifespan and aging-associated changes in cardiac intracellular Ca2+ homeostasis, protein damage and apoptotic protein expression. Aging Cell 6:799–806. doi: 10.1111/j.1474-9726.2007.00343.x · DOI
  36. Li Q, Wu S, Li SY, Lopez FL, Du M, Kajstura J, Anversa P, Ren J (2007) Cardiac-specific overexpression of insulin-like growth factor 1 attenuates aging-associated cardiac diastolic contractile dysfunction and protein damage. Am J Physiol Heart Circ Physiol 292:H1398–H1403. doi: 10.1152/ajpheart.01036.2006 · DOI
  37. Ma H, Guo R, Yu L, Zhang Y, Ren J (2011) Aldehyde dehydrogenase 2 (ALDH2) rescues myocardial ischaemia/reperfusion injury: role of autophagy paradox and toxic aldehyde. Eur Heart J 32:1025–1038. doi: 10.1093/eurheartj/ehq253 · DOI
  38. Matarrese P, Nencioni L, Checconi P, Ciarlo L, Gambardella L, Ascione B, Sgarbanti R, Garaci E, Malorni W, Palamara AT (2011) Pepstatin a alters host cell autophagic machinery and leads to a decrease in influenza a virus production. J Cell Physiol. doi: 10.1002/jcp.22696 · DOI
  39. Matsui T, Li L, Wu JC, Cook SA, Nagoshi T, Picard MH, Liao R, Rosenzweig A (2002) Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart. J Biol Chem 277:22896–22901. doi: 10.1074/jbc.M200347200 · DOI
  40. Matsui T, Nagoshi T, Hong EG, Luptak I, Hartil K, Li L, Gorovits N, Charron MJ, Kim JK, Tian R, Rosenzweig A (2006) Effects of chronic Akt activation on glucose uptake in the heart. Am J Physiol Endocrinol Metab 290:E789–E797. doi: 10.1152/ajpendo.00564.2004 · DOI
  41. Miyamoto S, Murphy AN, Brown JH (2009) Akt mediated mitochondrial protection in the heart: metabolic and survival pathways to the rescue. J Bioenerg Biomembr 41:169–180. doi: 10.1007/s10863-009-9205-y · DOI
  42. Nagoshi T, Matsui T, Aoyama T, Leri A, Anversa P, Li L, Ogawa W, del Monte F, Gwathmey JK, Grazette L, Hemmings BA, Kass DA, Champion HC, Rosenzweig A (2005) PI3K rescues the detrimental effects of chronic Akt activation in the heart during ischemia/reperfusion injury. J Clin Invest 115:2128–2138. doi: 10.1172/JCI23073 · DOI
  43. Oudit GY, Penninger JM (2009) Cardiac regulation by phosphoinositide 3-kinases and PTEN. Cardiovasc Res 82:250–260. doi: 10.1093/cvr/cvp014 · DOI
  44. Penna C, Tullio F, Perrelli MG, Moro F, Abbadessa G, Piccione F, Carriero V, Racca S, Pagliaro P (2011) Ischemia/reperfusion injury is increased and cardioprotection by a postconditioning protocol is lost as cardiac hypertrophy develops in nandrolone treated rats. Basic Res Cardiol 106:409–420. doi: 10.1007/s00395-010-0143-y · DOI
  45. Qian J, Ren X, Wang X, Zhang P, Jones WK, Molkentin JD, Fan GC, Kranias EG (2009) Blockade of Hsp20 phosphorylation exacerbates cardiac ischemia/reperfusion injury by suppressed autophagy and increased cell death. Circ Res 105:1223–1231. doi: 10.1161/CIRCRESAHA.109.200378 · DOI
  46. Ronnebaum SM, Patterson C (2010) The FoxO family in cardiac function and dysfunction. Annu Rev Physiol 72:81–94. doi: 10.1146/annurev-physiol-021909-135931 · DOI
  47. Sarkar S, Ravikumar B, Floto RA, Rubinsztein DC (2009) Rapamycin and mTOR-independent autophagy inducers ameliorate toxicity of polyglutamine-expanded huntingtin and related proteinopathies. Cell Death Differ 16:46–56. doi: 10.1038/cdd.2008.110 · DOI · Paper page
  48. Shinmura K, Tamaki K, Sano M, Murata M, Yamakawa H, Ishida H, Fukuda K (2011) Impact of long-term caloric restriction on cardiac senescence: caloric restriction ameliorates cardiac diastolic dysfunction associated with aging. J Mol Cell Cardiol 50:117–127. doi: 10.1016/j.yjmcc.2010.10.018 · DOI
  49. Simonsen A, Cumming RC, Brech A, Isakson P, Schubert DR, Finley KD (2008) Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4:176–184 · DOI · Paper page
  50. Sussman MA, Anversa P (2004) Myocardial aging and senescence: where have the stem cells gone? Annu Rev Physiol 66:29–48. doi: 10.1146/annurev.physiol.66.032102.140723 · DOI
  51. Toth ML, Sigmond T, Borsos E, Barna J, Erdelyi P, Takacs-Vellai K, Orosz L, Kovacs AL, Csikos G, Sass M, Vellai T (2008) Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 4:330–338 · DOI
  52. Vettor R, Fabris R, Serra R, Lombardi AM, Tonello C, Granzotto M, Marzolo MO, Carruba MO, Ricquier D, Federspil G, Nisoli E (2002) Changes in FAT/CD36, UCP2, UCP3 and GLUT4 gene expression during lipid infusion in rat skeletal and heart muscle. Int J Obes Relat Metab Disord 26:838–847. doi: 10.1038/sj.ijo.0802005 · DOI
  53. Wei JY (1992) Age and the cardiovascular system. N Engl J Med 327:1735–1739. doi: 10.1056/NEJM199212103272408 · DOI
  54. Wohlgemuth SE, Julian D, Akin DE, Fried J, Toscano K, Leeuwenburgh C, Dunn WA Jr (2007) Autophagy in the heart and liver during normal aging and calorie restriction. Rejuvenation Res 10:281–292. doi: 10.1089/rej.2006.0535 · DOI · Paper page
  55. Yang X, Doser TA, Fang CX, Nunn JM, Janardhanan R, Zhu M, Sreejayan N, Quinn MT, Ren J (2006) Metallothionein prolongs survival and antagonizes senescence-associated cardiomyocyte diastolic dysfunction: role of oxidative stress. FASEB J 20:1024–1026. doi: 10.1096/fj.05-5288fje · DOI
  56. Yang X, Sreejayan N, Ren J (2005) Views from within and beyond: narratives of cardiac contractile dysfunction under senescence. Endocrine 26:127–137. doi: 10.1385/ENDO:26:2:127 · DOI
  57. Yitzhaki S, Huang C, Liu W, Lee Y, Gustafsson AB, Mentzer RM Jr, Gottlieb RA (2009) Autophagy is required for preconditioning by the adenosine A1 receptor-selective agonist CCPA. Basic Res Cardiol 104:157–167. doi: 10.1007/s00395-009-0006-6 · DOI
  58. Zhang C, Cuervo AM (2008) Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med 14:959–965. doi: 10.1038/nm.1851 · DOI · Paper page
  59. Zhang Y, Ren J (2010) Autophagy in ALDH2-elicited cardioprotection against ischemic heart disease: slayer or savior? Autophagy 6:1212–1213. doi: 10.4161/auto.6.8.13652 · DOI
  60. Zhang Y, Zeng Y, Wang M, Tian C, Ma X, Chen H, Fang Q, Jia L, Du J, Li H (2011) Cardiac-specific overexpression of E3 ligase Nrdp1 increases ischemia and reperfusion-induced cardiac injury. Basic Res Cardiol 106:371–383. doi: 10.1007/s00395-011-0157-0 · DOI

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Metadata

Authors
Hua, Y., Zhang, Y., Ceylan-Isik, A. F., Wold, L. E., Nunn, J. M., & Ren, J.
Venue
Basic Research in Cardiology
Publisher
Springer Science and Business Media LLC
Published
2011-09-09
Volume
106
Issue
6
Pages
1173-1191
ISSN
  • 0300-8428
  • 1435-1803
DOI
10.1007/s00395-011-0222-8
Cited by
178
References
6
Language
en
Licence
www.springer.com/tdm (tdm)

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CoChat. (2026). Citation check: Chronic akt activation accentuates aging-induced cardiac hypertrophy and myocardial contractile dysfunction: role of autophagy. https://app.cochat.ai/papers/10.1007/s00395-011-0222-8
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Hua, Y., Zhang, Y., Ceylan-Isik, A. F., Wold, L. E., Nunn, J. M., & Ren, J. (2011). Chronic akt activation accentuates aging-induced cardiac hypertrophy and myocardial contractile dysfunction: role of autophagy. Basic Research in Cardiology. https://doi.org/10.1007/s00395-011-0222-8