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Heart Failure pp 131–160Cite as

Signaling Cascades in Heart Failure: From Cardiomyocytes Growth and Survival to Mitochondrial Signaling Pathways

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Part of the book series: Contemporary Cardiology ((CONCARD))

Abstract

Over the last decade, signal transduction pathways have been identified in normal cardiovascular growth processes, metabolic homeostasis, and during the development of the myocardium and vasculature. Alterations in discrete components of these signaling pathways are contributory factors in the pathogenesis and progression of a broad spectrum of cardiovascular disorders, dysrhythmias, atherosclerosis, hypertension, diabetes, and metabolic syndrome, and in the cardiovascular dysfunction associated with aging, as well as heart failure (HF).

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References

  1. Engel FB, Schebesta M, Duong MT, Lu G, Ren S, Madwed JB, Jiang H, Wang Y, Keating MT (2005) p38 MAP kinase inhibition enables proliferation of adult mammalian cardiomyocytes. Genes Dev 19:1175–1187

    Article  PubMed  CAS  Google Scholar 

  2. Tamamori-Adachi M, Ito H et al. (2003) Critical role of cyclin D1 nuclear import in cardiomyocyte proliferation. Circ Res 92:e12–e19

    Article  PubMed  CAS  Google Scholar 

  3. Pasumarthi KB, Kardami E, Cattini PA (1996) High and low molecular weight fibroblast growth factor-2 increase proliferation of neonatal rat cardiac myocytes but have differential effects on binucleation and nuclear morphology. Evidence for both paracrine and intracrine actions of fibroblast growth factor-2. Circ Res 78:126–136

    Article  PubMed  CAS  Google Scholar 

  4. Sheikh F, Jin Y, Pasumarthi KB, Kardami E, Cattini PA (1997) Expression of fibroblast growth factor receptor-1 in rat heart H9c2 myoblasts increases cell proliferation. Mol Cell Biochem 176:89–97

    Article  PubMed  CAS  Google Scholar 

  5. Sheng Z, Pennica D, Wood WI, Chien KR (1996) Cardiotrophin-1 displays early expression in the murine heart tube and promotes cardiac myocyte survival. Development 122:419–428

    PubMed  CAS  Google Scholar 

  6. Kuwahara K, Saito Y, Kishimoto I et al (2000) Cardiotrophin-1 phosphorylates akt and BAD, and prolongs cell survival via a PI3K-dependent pathway in cardiac myocytes. J Mol Cell Cardiol 32:1385–1394

    Article  PubMed  CAS  Google Scholar 

  7. Huss JM, Kelly DP (2005) Mitochondrial energy metabolism in heart failure: a question of balance. J Clin Invest 115:547–555

    PubMed  CAS  Google Scholar 

  8. Shiojima I, Walsh K (2006) Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway. Genes Dev 20:3347–3365

    Article  PubMed  CAS  Google Scholar 

  9. Sugden PH (2003) Ras, Akt, and mechanotransduction in the cardiac myocyte. Circ Res 93:1179–1192

    Article  PubMed  CAS  Google Scholar 

  10. Chesley A, Lundberg MS, Asai T, Xiao RP, Ohtani S, Lakatta EG, Crow MT (2000) The beta(2)-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G(i)-dependent coupling to phosphatidylinositol 3′-kinase. Circ Res 87:1172–1179

    Article  PubMed  CAS  Google Scholar 

  11. Ananthakrishnan R, Gordon WM, Goldenthal MJ, Marín-García J (2005) Akt signaling pathway in pacing-induced heart failure. Mol Cell Biochem 268:103–110

    Article  PubMed  CAS  Google Scholar 

  12. Pham FH, Sugden PH, Clerk A (2000) Regulation of protein kinase B and 4E-BP1 by oxidative stress in cardiac myocytes. Circ Res 86:1252–1258

    Article  PubMed  CAS  Google Scholar 

  13. Recchia FA, McConnell PI, Bernstein RD, Vogel TR, Xu X, Hintze TH (1998) Reduced nitric oxide production and altered myocardial metabolism during the decompensation of pacing-induced heart failure in the conscious dog. Circ Res 83:969–979

    Article  PubMed  CAS  Google Scholar 

  14. Osorio JC, Stanley WC, Linke A et al (2002) Impaired myocardial fatty oxidation and reduced protein expression of retinoid X receptor-alpha in pacing – induced heart failure. Circulation 106:606–612

    Article  PubMed  CAS  Google Scholar 

  15. Sack MN, Rader TA, Park S, Bastin J, McCune SA, Kelly DP (1996) Fatty acid oxidation enzyme gene expression is down regulated in the failing heart. Circulation 94:2837–2842

    Article  PubMed  CAS  Google Scholar 

  16. Cook SA, Matsui T, Li L, Rosenzweig A (2002) Transcriptional effects of chronic Akt activation in the heart. J Biol Chem 277:22528–22533

    Article  PubMed  CAS  Google Scholar 

  17. 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

    Article  PubMed  CAS  Google Scholar 

  18. Qin S, Chock PB (2003) Implication of phosphatidylinositol 3-kinase membrane recruitment in hydrogen peroxide-induced activation of PI3K and Akt. Biochemistry 42:2995–3003

    Article  PubMed  CAS  Google Scholar 

  19. Gudz T, Tserng K, Hoppel DL (1997) Direct inhibition of mitochondrial respiratory chain complex III by cell-permeable ceramide. J Biol Chem 272:24154–24158

    Article  PubMed  CAS  Google Scholar 

  20. Datta SR, Dudek H, Tao X, Masters S, Fu H, Gotoh Y, Greenberg ME (1997) Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91:231–241

    Article  PubMed  CAS  Google Scholar 

  21. Liu W, Akhand AA, Takeda K, Kawamoto Y, Itoigawa M, Kato M, Suzuki H, Ishikawa N, Nakashima I (2003) Protein phosphatase 2A-linked and -unlinked caspase-dependent pathways for downregulation of Akt kinase triggered by 4-hydroxynonenal. Cell Death Differ 10:772–781

    Article  PubMed  CAS  Google Scholar 

  22. Kageyama K, Ihara Y, Goto S, Urata Y, Toda G, Yano K, Kondo T (2002) Overexpression of calreticulin modulates protein kinase B/Akt signaling to promote apoptosis during cardiac differentiation of cardiomyoblast H9c2 cells. J Biol Chem 277:19255–19264

    Article  PubMed  CAS  Google Scholar 

  23. Neumann J, Eschenhagen T, Jones LR, Linck B, Schmitz W, Scholz H, Zimmermann N (1997) Increased expression of cardiac phosphatases in patients with end-stage heart failure. J Mol Cell Cardiol 29:265–272

    Article  PubMed  CAS  Google Scholar 

  24. Nikolaidis LA, Sturzu A, Stolarski C, Elahi D, Shen YT, Shannon RP (2004) The development of myocardial insulin resistance in conscious dogs with advanced dilated cardiomyopathy. Cardiovasc Res 61:297–306

    Article  PubMed  CAS  Google Scholar 

  25. Matsui T, Li L, del Monte F, Fukui Y, Fukui Y, Franke TF, Hajjar RJ, Rosenzweig A (1999) adenoviral gene transfer of activated phospatidyl inositol 3- kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro. Circulation 100:2373–2379

    Article  PubMed  CAS  Google Scholar 

  26. McMullen JR, Shioi T, Huang WY, Zhang L, Tarnavski O, Bisping E, Schinke M, Kong S, Sherwood MC, Brown J, Riggi L, Kang PM, Izumo S (2004) The insulin-like growth factor 1 receptor induces physiological heart growth via the phosphoinositide 3-kinase (p110alpha ) pathway. J Biol Chem 279:4782–4793

    Article  PubMed  CAS  Google Scholar 

  27. Soltys CL, Buchholz L, Gandhi M, Clanachan AS, Walsh K, Dyck JR (2002) Phosphorylation of cardiac protein kinase B is regulated by palmitate. Am J Physiol Heart Circ Physiol 283:H1056–H1064

    PubMed  CAS  Google Scholar 

  28. Leslie NR, Bennett D, Lindsay YE, Sterwart H, Gray A, Downes CP (2003) Redox regulation of PI 3-kinase signalling via inactivation of PTEN. EMBO J 22:5501–5510

    Article  PubMed  CAS  Google Scholar 

  29. Dorn GW 2nd, Force T (2005) Protein kinase cascades in the regulation of cardiac hypertrophy. J Clin Invest 115:527–537

    PubMed  CAS  Google Scholar 

  30. Stokoe D, Stephens LR, Copeland T et al (1997) Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B. Science 277:567–570

    Article  PubMed  CAS  Google Scholar 

  31. Sarbassov DD, Guertin DA, Ali SM, Sabatini DM (2005) Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307:1098–1101

    Article  PubMed  CAS  Google Scholar 

  32. Wang L, Wang X, Proud CG (2000) Activation of mRNA translation in rat cardiac myocytes by insulin involves multiple rapamycin-sensitive steps. Am J Physiol Heart Circ Physiol 278:H1056–H1068

    PubMed  CAS  Google Scholar 

  33. Gao X, Zhang Y, Arrazola P, Hino O, Kobayashi T, Yeung RS, Ru B, Pan D (2002) Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat Cell Biol 4:699–704

    Article  PubMed  CAS  Google Scholar 

  34. Marygold SJ, Leevers SJ (2002) Growth signaling: TSC takes its place. Curr Biol 12:R785–R787

    Article  PubMed  CAS  Google Scholar 

  35. Zhang Y, Gao X, Saucedo LJ, Ru B, Edgar BA, Pan D (2003) Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat Cell Biol 5:578–581

    Article  PubMed  CAS  Google Scholar 

  36. Tee AR, Manning BD, Roux PP, Cantley LC, Blenis J (2003) Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Curr Biol 13:1259–1268

    Article  PubMed  CAS  Google Scholar 

  37. Badorff C, Ruetten H, Mueller S et al (2002) Fas receptor signaling inhibits glycogen synthase kinase 3 beta and induces cardiac hypertrophy following pressure overload. J Clin Invest 109:373–381

    PubMed  CAS  Google Scholar 

  38. Haq S, Choukroun G, Kang ZB et al (2000) Glycogen synthase kinase-3beta is a negative regulator of cardiomyocyte hypertrophy. J Cell Biol 151:117–130

    Article  PubMed  CAS  Google Scholar 

  39. Morisco C, Zebrowski D, Condorelli G, Tsichlis P, Vatner SF, Sadoshima J (2000) The Akt-glycogen synthase kinase 3beta pathway regulates transcription of atrial natriuretic factor induced by beta-adrenergic receptor stimulation in cardiac myocytes. J Biol Chem 275:14466–14475

    Article  PubMed  CAS  Google Scholar 

  40. Proud CG (2004) Ras, PI3-kinase and mTOR signaling in cardiac hypertrophy. Cardiovasc Res 63:403–413

    Article  PubMed  CAS  Google Scholar 

  41. Haq S, Michael A, Andreucci M, Bhattacharya K, Dotto P, Walters B, Woodgett J, Kilter H, Force T (2003) Stabilization of beta-catenin by a Wnt-independent mechanism regulates cardiomyocyte growth. Proc Natl Acad Sci USA 100:4610–4615

    Article  PubMed  CAS  Google Scholar 

  42. Michael A, Haq S, Chen X, Hsich E, Cui L, Walters B, Shao Z, Bhattacharya K, Kilter H, Huggins G, Andreucci M, Periasamy M, Solomon RN, Liao R, Patten R, Molkentin JD, Force T (2004) Glycogen synthase kinase-3beta regulates growth, calcium homeostasis, and diastolic function in the heart. J Biol Chem 279:21383–21393

    Article  PubMed  CAS  Google Scholar 

  43. Liao W, Wang S, Han C, Zhang Y (2005) 14-3-3 proteins regulate glycogen synthase 3beta phosphorylation and inhibit cardiomyocyte hypertrophy. FEBS J 272:1845–1854

    Article  PubMed  CAS  Google Scholar 

  44. Chan AY, Soltys CL, Young ME, Proud CG, Dyck JR (2004) Activation of AMP-activated protein kinase inhibits protein synthesis associated with hypertrophy in the cardiac myocyte. J Biol Chem 279:32771–32779

    Article  PubMed  CAS  Google Scholar 

  45. Arsham AM, Howell JJ, Simon MC (2003) A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets. J Biol Chem 278:29655–29660

    Article  PubMed  CAS  Google Scholar 

  46. van Noort M, Meeldijk J, van der Zee R, Destree O, Clevers H (2002) Wnt signaling controls the phosphorylation status of beta-catenin. J Biol Chem 277:17901–17905

    Article  PubMed  CAS  Google Scholar 

  47. Aikawa R, Nawano M, Gu Y, Katagiri H, Asano T, Zhu W, Nagai R, Komuro I (2000) Insulin prevents cardiomyocytes from oxidative stress-induced apoptosis through activation of PI3 kinase/Akt. Circulation 102:2873–2879

    Article  PubMed  CAS  Google Scholar 

  48. Gao F, Gao E, Yue TL, Ohlstein EH, Lopez BL, Christopher TA, Ma XL (2002) Nitric oxide mediates the antiapoptotic effect of insulin in myocardial ischemia-reperfusion: the roles of PI3-kinase, Akt, and endothelial nitric oxide synthase phosphorylation. Circulation 105:1497–1502

    Article  PubMed  CAS  Google Scholar 

  49. Matsui T, Li L, del Monte F, Fukui Y, Franke TF, Hajjar RJ, Rosenzweig A (1999) Adenoviral gene transfer of activated phosphatidylinositol 3′-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro. Circulation 100:2373–2379

    Article  PubMed  CAS  Google Scholar 

  50. Yamashita K, Kajstura J, Discher DJ, Wasserlauf BJ, Bishopric NH, Anversa P, Webster KA (2001) Reperfusion-activated Akt kinase prevents apoptosis in transgenic mouse hearts overexpressing insulin-like growth factor-1. Circ Res 88:609–614

    Article  PubMed  CAS  Google Scholar 

  51. Craig R, Wagner M, McCardle T, Craig AG, Glembotski CC (2001) The cytoprotective effects of the glycoprotein 130 receptor-coupled cytokine, cardiotrophin-1, require activation of NF-kappa B. J Biol Chem 276:37621–37629

    Article  PubMed  CAS  Google Scholar 

  52. Negoro S, Oh H, Tone E, Kunisada K, Fujio Y, Walsh K, Kishimoto T, Yamauchi-Takihara K (2001) Glycoprotein 130 regulates cardiac myocyte survival in doxorubicin-induced apoptosis through phosphatidylinositol 3-kinase/Akt phosphorylation and Bcl-xL/caspase-3 interaction. Circulation 103:555–561

    Article  PubMed  CAS  Google Scholar 

  53. Tian B, Liu J, Bitterman P, Bache RJ (2003) Angiotensin II modulates nitric oxide-induced cardiac fibroblast apoptosis by activation of AKT/PKB. Am J Physiol Heart Circ Physiol 285:H1105–H1112

    PubMed  CAS  Google Scholar 

  54. Clerk A, Sugden PH (1999) Activation of protein kinase cascades in the heart by hypertrophic G protein-coupled receptor agonists. Am J Cardiol 83:64H–69H

    Article  PubMed  CAS  Google Scholar 

  55. Krieg T, Landsberger M, Alexeyev MF, Felix SB, Cohen MV, Downey JM (2003) Activation of Akt is essential for acetylcholine to trigger generation of oxygen free radicals. Cardiovasc Res 58:196–202

    Article  PubMed  CAS  Google Scholar 

  56. Yin H, Chao L, Chao J (2004) Adrenomedullin protects against myocardial apoptosis after ischemia/reperfusion through activation of Akt-GSK signaling. Hypertension 43:109–116

    Article  PubMed  CAS  Google Scholar 

  57. Naga Prasad SV, Esposito G, Mao L, Koch WJ, Rockman HA (2000) Gbetagamma-dependent phosphoinositide 3-kinase activation in hearts with in vivo pressure overload hypertrophy. J Biol Chem 275:4693–4698

    Article  PubMed  CAS  Google Scholar 

  58. Mockridge JW, Marber MS, Heads RJ (2000) Activation of Akt during simulated ischemia/reperfusion in cardiac myocytes. Biochem Biophys Res Commun 270:947–952

    Article  PubMed  CAS  Google Scholar 

  59. Condorelli G, Drusco A, Stassi G et al (2002) Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice. Proc Natl Acad Sci USA 99:12333–12338

    Article  PubMed  CAS  Google Scholar 

  60. Liu Tj, Lai Hc, Wu W, Chinn S, Wang PH (2001) Developing a strategy to define the effects of insulin-like growth factor-1 on gene expression profile in cardiomyocytes. Circ Res 88:1231–1238

    Article  CAS  Google Scholar 

  61. Bialik S, Cryns VL, Drincic A, Miyata S, Wollowick AL, Srinivasan A, Kitsis RN (1999) The mitochondrial apoptotic pathway is activated by serum and glucose deprivation in cardiac myocytes. Circ Res 85:403–414

    Article  PubMed  CAS  Google Scholar 

  62. Edinger AL, Thompson CB (2002) Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake. Mol Biol Cell 13:2276–2288

    Article  PubMed  CAS  Google Scholar 

  63. Juhaszova M, Zorov DB, Kim SH et al (2004) Glycogen synthase kinase-3beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113:1535–1549

    PubMed  CAS  Google Scholar 

  64. Conti E, Musumeci MB, Assenza GE, Quarta G, Autore C, Volpe M (2008) Recombinant human insulin-like growth factor-1: a new cardiovascular disease treatment option? Cardiovasc Hematol Agents Med Chem 6:258–271

    Article  PubMed  CAS  Google Scholar 

  65. Noguchi S, Kashihara Y, Ikegami Y, Morimoto K, Miyamoto M, Nakao K (1993) Insulin-like growth factor-I ameliorates transient ischemia-induced acute renal failure in rats. J Pharmacol Exp Ther 267:919–926

    PubMed  CAS  Google Scholar 

  66. Gluckman P, Klempt N, Guan J, Mallard C, Sirimanne E, Dragunow M, Klempt M, Singh K, Williams C, Nikolics K (1992) A role for IGF-1 in the rescue of CNS neurons following hypoxic-ischemic injury. Biochem Biophys Res Commun 182:593–599

    Article  PubMed  CAS  Google Scholar 

  67. Buerke M, Murohara T, Skurk C, Nuss C, Tomaselli K, Lefer AM (1995) Cardioprotective effect of insulin-like growth factor I in myocardial ischemia followed by reperfusion. Proc Natl Acad Sci USA 92:8031–8035

    Article  PubMed  CAS  Google Scholar 

  68. Davani EY, Brumme Z, Singhera GK, Cote HC, Harrigan PR, Dorscheid DR (2003) Insulin-like growth factor-1 protects ischemic murine myocardium from ischemia/reperfusion associated injury. Crit Care 7:R176–R183

    Article  PubMed  Google Scholar 

  69. Otani H, Yamamura T, Nakao Y, Hattori R, Kawaguchi H, Osako M, Imamura H (2000) Insulin-like growth factor-I improves recovery of cardiac performance during reperfusion in isolated rat heart by a wortmannin-sensitive mechanism. J Cardiovasc Pharmacol 35:275–281

    Article  PubMed  CAS  Google Scholar 

  70. Friehs I, Stamm C, Cao-Danh H, McGowan FX, del Nido PJ (2001) Insulin-like growth factor-1 improves postischemic recovery in hypertrophied hearts. Ann Thorac Surg 72:1650–1656

    Article  PubMed  CAS  Google Scholar 

  71. Yamamura T, Otani H, Nakao Y, Hattori R, Osako M, Imamura H (2001) IGF-I differentially regulates Bcl-xL and Bax and confers myocardial protection in the rat heart. Am J Physiol Heart Circ Physiol 280:H1191–H1200

    PubMed  CAS  Google Scholar 

  72. Li Q, Li B, Wang X, Leri A, Jana KP, Liu Y et al (1997) Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy. J Clin Invest 100:1991–1999

    Article  PubMed  CAS  Google Scholar 

  73. Fujio Y, Nguyen T, Wencker D, Kitsis RN, Walsh K (2000) Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation 101:660–667

    Article  PubMed  CAS  Google Scholar 

  74. Ren J, Samson WK, Sowers JR (1999) Insulin-like growth factor I as a cardiac hormone: physiological and pathophysiological implications in heart disease. J Mol Cell Cardiol 31:2049–2061

    Article  PubMed  CAS  Google Scholar 

  75. Lai HC, Liu TJ, Ting CT, Sharma PM, Wang PH (2003) Insulin-like growth factor-1 prevents loss of electrochemical gradient in cardiac muscle mitochondria via activation of PI 3 kinase/Akt pathway. Mol Cell Endocrinol 205:99–106

    Article  PubMed  CAS  Google Scholar 

  76. Foncea R, Andersson M, Ketterman A, Blakesley V, Sapag-Hagar M, Sugden PH, LeRoith D, Lavandero S (1997) Insulin-like growth factor-I rapidly activates multiple signal transduction pathways in cultured rat cardiac myocytes. J Biol Chem 272:19115–19124

    Article  PubMed  CAS  Google Scholar 

  77. Vander Heiden MG, Chandel NS, Williamson EK, Schumacker PT, Thompson CB (1997) Bcl-xL regulates the membrane potential and volume homeostasis of mitochondria. Cell 91:627–637

    Article  PubMed  CAS  Google Scholar 

  78. Juhaszova M, Zorov DB, Kim SH, Pepe S, Fu Q, Fishbein KW, Ziman BD, Wang S, Ytrehus K, Antos CL, Olson EN, Sollott SJ (2004) Glycogen synthase kinase-3 beta mediates convergence of protection signaling to inhibit the mitochondrial permeability transition pore. J Clin Invest 113:1535–1549

    PubMed  CAS  Google Scholar 

  79. Chao W, Matsui T, Novikov MS, Tao J, Li L, Liu H, Ahn Y, Rosenzweig A (2003) Strategic advantages of insulin-like growth factor-I expression for cardioprotection. J Gene Med 5:277–286

    Article  PubMed  CAS  Google Scholar 

  80. Pi Y, Goldenthal MJ, Marín-García J (2007) Mitochondrial involvement in IGF-1 induced protection of cardiomyocytes against hypoxia/reoxygenation injury. Mol Cell Biochem 301:181–189

    Article  PubMed  CAS  Google Scholar 

  81. Welch S, Plank D, Witt S et al (2002) Cardiac-specific IGF-1 expression attenuates dilated cardiomyopathy in tropomodulin-overexpressing transgenic mice. Circ Res 90:641–648

    Article  PubMed  CAS  Google Scholar 

  82. Kennedy BK, Austriaco NR Jr, Zhang J, Guarente L (1995) Mutation in the silencing gene SIR4 can delay aging in S. cerevisiae. Cell 80:485–496

    Article  PubMed  CAS  Google Scholar 

  83. Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13:2570–2580

    Article  PubMed  CAS  Google Scholar 

  84. Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410:227–230

    Article  PubMed  CAS  Google Scholar 

  85. Rine J, Herskowitz I (1987) Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae. Genetics 116:9–22

    PubMed  CAS  Google Scholar 

  86. Sinclair DA, Guarente L (1997) Extrachromosomal rDNA circles – a cause of aging in yeast. Cell 91:1033–1042

    Article  PubMed  CAS  Google Scholar 

  87. Lin SJ, Ford E, Haigis M, Liszt G, Guarente L (2004) Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev 18:12–16

    Article  PubMed  CAS  Google Scholar 

  88. Alcendor RR, Kirshenbaum LA, Imai S, Vatner SF, Sadoshima J (2004) Silent information regulator 2alpha, a longevity factor and class III histone deacetylase, is an essential endogenous apoptosis inhibitor in cardiac myocytes. Circ Res 95:971–980

    Article  PubMed  CAS  Google Scholar 

  89. Pillai JB, Isbatan A, Imai S, Gupta MP (2005) Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. J Biol Chem 280:43121–43130

    Article  PubMed  CAS  Google Scholar 

  90. Motta MC, Divecha N, Lemieux M et al (2004) Mammalian SIRT1 represses forkhead transcription factors. Cell 116:551–563

    Article  PubMed  CAS  Google Scholar 

  91. Brunet A, Sweeney LB, Sturgill JF et al (2004) Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science 303:2011–2015

    Article  PubMed  CAS  Google Scholar 

  92. Daitoku H, Hatta M, Matsuzaki H, Aratani S, Ohshima T, Miyagishi M, Nakajima T, Fukamizu A (2004) Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity. Proc Natl Acad Sci USA 101:10042–10047

    Article  PubMed  CAS  Google Scholar 

  93. Wang C, Chen L, Hou X et al (2006) Interactions between E2F1 and SirT1 regulate apoptotic response to DNA damage. Nat Cell Biol 8:1025–1031

    Article  PubMed  CAS  Google Scholar 

  94. Nemoto S, Fergusson MM, Finkel T (2005) SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}. J Biol Chem 280:16456–16460

    Article  PubMed  CAS  Google Scholar 

  95. Bouras T, Fu M, Sauve AA, Wang F, Quong AA, Perkins ND, Hay RT, Gu W, Pestell RG (2005) SIRT1 deacetylation and repression of p300 involves lysine residues 1020/1024 within the cell cycle regulatory domain 1. J Biol Chem 280:10264–10276

    Article  PubMed  CAS  Google Scholar 

  96. Yang T, Fu M, Pestell R, Sauve AA (2006) SIRT1 and endocrine signaling. Trends Endocrinol Metab 17:186–191

    Article  PubMed  CAS  Google Scholar 

  97. Seymour EM, Parikh RV, Singer AA, Bolling SF (2006) Moderate calorie restriction improves cardiac remodeling and diastolic dysfunction in the Dahl-SS rat. J Mol Cell Cardiol 41:661–668

    Article  PubMed  CAS  Google Scholar 

  98. Rogina B, Helfand SL (2004) Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc Natl Acad Sci USA 101:15998–16003

    Article  PubMed  CAS  Google Scholar 

  99. Chen D, Steele AD, Lindquist S, Guarente L (2005) Increase in activity during calorie restriction requires Sirt1. Science 310:1641

    Article  PubMed  CAS  Google Scholar 

  100. Picard F, Kurtev M, Chung N et al (2004) Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma. Nature 429:771–776

    Article  PubMed  CAS  Google Scholar 

  101. Lee CK, Allison DB, Brand J, Weindruch R, Prolla TA (2002) Transcriptional profiles associated with aging and middle age-onset caloric restriction in mouse hearts. Proc Natl Acad Sci USA 99:14988–14993

    Article  PubMed  CAS  Google Scholar 

  102. Kaeberlein M, Powers RW 3rd, Steffen KK et al (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310:1193–1196

    Article  PubMed  CAS  Google Scholar 

  103. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14:885–890

    Article  PubMed  CAS  Google Scholar 

  104. Powers RW 3rd, Kaeberlein M, Caldwell SD, Kennedy BK, Fields S (2006) Extension of chronological life span in yeast by decreased TOR pathway signaling. Genes Dev 20:174–184

    Article  PubMed  CAS  Google Scholar 

  105. Desai BN, Myers BR, Schreiber SL (2002) FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction. Proc Natl Acad Sci USA 99:4319–4324

    Article  PubMed  CAS  Google Scholar 

  106. Kim DH, Sarbassov DD, Ali SM, King JE, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM (2002) mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110:163–175

    Article  PubMed  CAS  Google Scholar 

  107. Tokunaga C, Yoshino K, Yonezawa K (2004) mTOR integrates amino acid- and energy-sensing pathways. Biochem Biophys Res Commun 313:443–446

    Article  PubMed  CAS  Google Scholar 

  108. Nojima H, Tokunaga C, Eguchi S et al (2003) The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem 278:15461–15464

    Article  PubMed  CAS  Google Scholar 

  109. Schieke SM, Phillips D, McCoy JP Jr, Aponte AM, Shen RF, Balaban RS, Finkel T (2006) The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J Biol Chem 281:27643–27652

    Article  PubMed  CAS  Google Scholar 

  110. Khan S, Salloum F, Das A, Xi L, Vetrovec GW, Kukreja RC (2006) Rapamycin confers preconditioning-like protection against ischemia-reperfusion injury in isolated mouse heart and cardiomyocytes. J Mol Cell Cardiol 41:256–264

    Article  PubMed  CAS  Google Scholar 

  111. Shioi T, McMullen JR, Tarnavski O, Converso K, Sherwood MC, Manning WJ, Izumo S (2003) Rapamycin attenuates load-induced cardiac hypertrophy in mice. Circulation 107:1664–1670

    Article  PubMed  CAS  Google Scholar 

  112. McMullen JR, Sherwood MC, Tarnavski O, Zhang L, Dorfman AL, Shioi T, Izumo S (2004) Inhibition of mTOR signaling with rapamycin regresses established cardiac hypertrophy induced by pressure overload. Circulation 109:3050–3055

    Article  PubMed  CAS  Google Scholar 

  113. Flagg TP, Nichols CG (2005) Sarcolemmal K(ATP) channels: what do we really know? J Mol Cell Cardiol 39:61–70

    Article  PubMed  CAS  Google Scholar 

  114. Scarpulla RC (2002) Nuclear activators and coactivators in mammalian mitochondrial biogenesis. Biochim Biophys Acta 1576:1–14

    Article  PubMed  CAS  Google Scholar 

  115. Goffart S, Wiesner RJ (2003) Regulation and co-ordination of nuclear gene expression during mitochondrial biogenesis. Exp Physiol 88:33–40

    Article  PubMed  CAS  Google Scholar 

  116. Xia Y, Buja LM, Scarpulla RC et al (1997) Electrical stimulation of neonatal cardio-myocytes results in sequential activation of nuclear genes governing mitochondrial proliferation and differentiation. Proc Natl Acad Sci USA 94:11399–11404

    Article  PubMed  CAS  Google Scholar 

  117. Lehman JJ, Barger PM, Kovacs A et al (2000) Peroxisome proliferator-activated receptor gamma coactivator-1 promotes cardiac mitochondrial biogenesis. J Clin Invest 106:847–856

    Article  PubMed  CAS  Google Scholar 

  118. Gilde AJ, van der Lee KA, Willemsen PH et al (2003) Peroxisome proliferator-activated receptor PPARalpha and PPARbeta/delta, but not PPARgamma, modulate the expression of genes involved in cardiac lipid metabolism. Circ Res 92:518–524

    Article  PubMed  CAS  Google Scholar 

  119. Barger PM, Kelly DP (2000) PPAR signaling in the control of cardiac energy metabolism. Trends Cardiovasc Med 10:238–245

    Article  PubMed  CAS  Google Scholar 

  120. Garnier A, Fortin D, Delomenie C et al (2003) Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles. J Physiol 551:491–501

    Article  PubMed  CAS  Google Scholar 

  121. Huss JM, Levy FH, Kelly DP (2001) Hypoxia inhibits the peroxisome proliferator-activated receptor alpha/retinoid X receptor gene regulatory pathway in cardiac myocytes: a mechanism for O2-dependent modulation of mitochondrial fatty acid oxidation. J Biol Chem 276:27605–27612

    Article  PubMed  CAS  Google Scholar 

  122. Wu H, Kanatous SB, Thurmond FA et al (2002) Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science 296:349–352

    Article  PubMed  CAS  Google Scholar 

  123. Sack MN, Harrington LS, Jonassen AK et al (2000) Coordinate regulation of metabolic enzyme encoding genes during cardiac development and following carvedilol therapy in spontaneously hypertensive rats. Cardiovasc Drugs Ther 14:31–39

    Article  PubMed  CAS  Google Scholar 

  124. Bushdid PB, Osinska H, Waclaw RR et al (2003) NFATc3 and NFATc4 are required for cardiac development and mitochondrial function. Circ Res 92:1305–1313

    Article  PubMed  CAS  Google Scholar 

  125. Finck BN, Lehman JJ, Leone TC et al (2002) The cardiac phenotype induced by PPARalpha overexpression mimics that caused by diabetes mellitus. J Clin Invest 109:121–130

    PubMed  CAS  Google Scholar 

  126. Wang J, Wilhelmsson H, Graff C et al (1999) Dilated cardiomyopathy and atrioventricular conduction blocks induced by heart-specific inactivation of mtDNA gene expression. Nat Genet 21:133–137

    Article  PubMed  CAS  Google Scholar 

  127. Rapizzi E, Pinton P, Szabadkai G, Wieckowski MR, Vandecasteele G, Baird G et al (2002) Recombinant expression of the voltage dependent anion channel enhances the transfer of Ca2+ microdomains to mitochondria. J Cell Biol 159:613–624

    Article  PubMed  CAS  Google Scholar 

  128. Casas F, Rochard P, Rodier A, Cassar-Malek I, Marchal-Victorion S, Wiesner RJ et al (1999) A variant form of the nuclear triiodothyronine receptor c-ErbAalpha1 plays a direct role in regulation of mitochondrial RNA synthesis. Mol Cell Biol 19:7913–7924

    PubMed  CAS  Google Scholar 

  129. Scheller K, Seibel P, Sekeris CE (2003) Glucocorticoid and thyroid hormone receptors in mitochondria of animal cells. Int Rev Cytol 222:1–61

    Article  PubMed  Google Scholar 

  130. Stadtman ER, Berlett BS (1998) Reactive oxygen-mediated protein oxidation in aging and disease. Drug Metab Rev 30:225–243

    Article  PubMed  CAS  Google Scholar 

  131. Choksi KB, Boylston WH, Rabek JP, Widger WR, Papaconstantinou J (2004) Oxidatively damaged proteins of heart mitochondrial electron transport complexes. Biochim Biophys Acta 1688:95–101

    Article  PubMed  CAS  Google Scholar 

  132. Vasquez-Vivar J, Kalyanaraman B, Kennedy MC (2000) Mitochondrial aconitase is a source of hydroxyl radical. An electron spin resonance investigation. J Biol Chem 275:14064–14069

    Article  PubMed  CAS  Google Scholar 

  133. Paradies G, Petrosillo G, Pistolese M, Ruggiero FM (2002) Reactive oxygen species affect mitochondrial electron transport complex I activity through oxidative cardiolipin damage. Gene 286:135–141

    Article  PubMed  CAS  Google Scholar 

  134. Petrosillo G, Ruggiero FM, Pistolese M, Paradies G (2001) Reactive oxygen species generated from the mitochondrial electron transport chain induce cytochrome c dissociation from beef-heart submitochondrial particles via cardiolipin peroxidation: possible role in the apoptosis. FEBS Lett 509:435–438

    Article  PubMed  CAS  Google Scholar 

  135. Wolin MS, Ahmad M, Gupte SA (2005) Oxidant and redox signaling in vascular oxygen sensing mechanisms: basic concepts, current controversies, and potential importance of cytosolic NADPH. Am J Physiol Lung Cell Mol Physiol 289:L159–L173

    Article  PubMed  CAS  Google Scholar 

  136. Brown GC (1999) Nitric oxide and mitochondrial respiration. Biochim Biophys Acta 1411:351–369

    Article  PubMed  CAS  Google Scholar 

  137. Murray J, Taylor SW, Zhang B, Ghosh SS, Capaldi RA (2003) Oxidative damage to mitochondrial complex I due to peroxynitrite: identification of reactive tyrosines by mass spectrometry. J Biol Chem 278:37223–37230

    Article  PubMed  CAS  Google Scholar 

  138. Riobo NA, Clementi E, Melani M, Boveris A, Cadenas E, Moncada S, Poderoso JJ (2001) Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation. Biochem J 359:139–145

    Article  PubMed  CAS  Google Scholar 

  139. Cassina AM, Hodara R, Souza JM, Thomson L, Castro L, Ischiropoulos H, Freeman BA, Radi R (2000) Cytochrome c nitration by peroxynitrite. J Biol Chem 275:21409–21415

    Article  PubMed  CAS  Google Scholar 

  140. Castro L, Rodriguez M, Radi R (1994) Aconitase is readily inactivated by peroxynitrite, but not by its precursor, nitric oxide. J Biol Chem 269:29409–29415

    PubMed  CAS  Google Scholar 

  141. Packer MA, Scarlett JL, Martin SW, Murphy MP (1997) Induction of the mitochondrial permeability transition by peroxynitrite. Biochem Soc Trans 25:909–914

    PubMed  CAS  Google Scholar 

  142. Brookes PS, Darley-Usmar VM (2004) Role of calcium and superoxide dismutase in sensitizing mitochondria to peroxynitrite-induced permeability transition. Am J Physiol Heart Circ Physiol 286:H39–H46

    Article  PubMed  CAS  Google Scholar 

  143. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW (1994) Angiotensin stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 74:1141–1148

    Article  PubMed  CAS  Google Scholar 

  144. De Keulenaer GW, Alexander RW, Ushio-Fukai M, Ishizaka N, Griendling KK (1998) Tumor necrosis factor activates a p22phox-based NADH oxidase in vascular smooth muscle. Biochem J 329:653–657

    PubMed  Google Scholar 

  145. Patterson C, Ruef J, Madamanchi NR, Barry-Lane P, Hu Z, Horaist C, Ballinger CA, Brasier AR, Bode C, Runge MS (1999) Stimulation of a vascular smooth muscle cell NAD(P)H oxidase by thrombin: evidence that p47phox may participate in forming this oxidase in vitro and in vivo. J Biol Chem 274:19814–19822

    Article  PubMed  CAS  Google Scholar 

  146. Hellsten-Westing Y (1993) Immunohistochemical localization of xanthine oxidase in human cardiac and skeletal muscle. Histochemistry 100:215–222

    Article  PubMed  CAS  Google Scholar 

  147. Cappola TP, Kass DA, Nelson GS, Berger RD, Rosas GO, Kobeissi ZA, Marban E, Hare JM (2001) Allopurinol improves myocardial efficiency in patients with idiopathic dilated cardiomyopathy. Circulation 104:2407–2411

    Article  PubMed  CAS  Google Scholar 

  148. Nemoto S, Takeda K, Yu ZX, Ferrans VJ, Finkel T (2000) Role for mitochondrial oxidants as regulators of cellular metabolism. Mol Cell Biol 20:7311–7318

    Article  PubMed  CAS  Google Scholar 

  149. Cadenas E (2004) Mitochondrial free radical production and cell signaling. Mol Aspects Med 25:17–26

    Article  PubMed  CAS  Google Scholar 

  150. Bogoyevitch MA, Ng DC, Court NW, Draper KA, Dhillon A (2000) Abas L Intact mitochondrial electron transport function is essential for signalling by hydrogen peroxide in cardiac myocytes. J Mol Cell Cardiol 32:1469–1480

    Article  PubMed  CAS  Google Scholar 

  151. Archer SL, Wu XC, Thebaud B, Moudgil R, Hashimoto K, Michelakis ED (2004) O2 sensing in the human ductus arteriosus: redox-sensitive K+ channels are regulated by mitochondria-derived hydrogen peroxide. Biol Chem 385:205–216

    Article  PubMed  CAS  Google Scholar 

  152. Yamamura T, Otani H, Nakao Y, Hattori R, Osako M, Imamura H, Das DK (2001) Dual involvement of coenzyme Q10 in redox signaling and inhibition of death signaling in the rat heart mitochondria. Antioxid Redox Signal 3:103–112

    Article  PubMed  CAS  Google Scholar 

  153. Brookes PS, Levonen AL, Shiva S, Sarti P, Darley-Usmar VM (2002) Mitochondria: regulators of signal transduction by reactive oxygen and nitrogen species. Free Radic Biol Med 33:755–764

    Article  PubMed  CAS  Google Scholar 

  154. Boveris A, D’Amico G, Lores-Arnaiz S, Costa LE (2003) Enalapril increases mitochondrial nitric oxide synthase activity in heart and liver. Antioxid Redox Signal 5:691–697

    Article  PubMed  CAS  Google Scholar 

  155. O’Rourke B (2000) Myocardial KATP channels in preconditioning. Circ Res 87:845–855

    Article  PubMed  Google Scholar 

  156. Lebuffe G, Schumacker PT, Shao ZH, Anderson T, Iwase H, Vanden Hoek TL (2003) ROS and NO trigger early preconditioning: relationship to mitochondrial KATP channel. Am J Physiol Heart Circ Physiol 284:H299–H308

    PubMed  CAS  Google Scholar 

  157. Oldenburg O, Cohen MV, Yellon DM, Downey JM (2002) Mitochondrial K(ATP) channels: role in cardioprotection. Cardiovasc Res 55:429–437

    Article  PubMed  CAS  Google Scholar 

  158. Ardehali H, O’Rourke B (2005) Mitochondrial K(ATP) channels in cell survival and death. J Mol Cell Cardiol 39:7–16

    Article  PubMed  CAS  Google Scholar 

  159. Garlid KD, Dos Santos P, Xie ZJ, Costa AD, Paucek P (2003) Mitochondrial potassium transport: the role of the mitochondrial ATP-sensitive K(+) channel in cardiac function and cardioprotection. Biochim Biophys Acta 1606:1–21

    Article  PubMed  CAS  Google Scholar 

  160. Das M, Parker JE, Halestrap AP (2003) Matrix volume measurements challenge the existence of diazoxide/glibencamide-sensitive KATP channels in rat mitochondria. J Physiol 547:893–902

    Article  PubMed  CAS  Google Scholar 

  161. Akao M, Teshima Y, Marban E (2002) Antiapoptotic effect of nicorandil mediated by mitochondrial atp-sensitive potassium channels in cultured cardiac myocytes. J Am Coll Cardiol 40:803–810

    Article  PubMed  CAS  Google Scholar 

  162. Nagata K, Obata K, Odashima M, Yamada A, Somura F, Nishizawa T, Ichihara S, Izawa H, Iwase M, Hayakawa A, Murohara T, Yokota M (2003) Nicorandil inhibits oxidative stress-induced apoptosis in cardiac myocytes through activation of mitochondrial ATP-sensitive potassium channels and a nitrate-like effect. J Mol Cell Cardiol 35:1505–1512

    Article  PubMed  CAS  Google Scholar 

  163. Xu W, Liu Y, Wang S, McDonald T, Van Eyk JE, Sidor A, O’Rourke B (2002) Cytoprotective role of Ca2+- activated K+ channels in the cardiac inner mitochondrial membrane. Science 298:1029–1033

    Article  PubMed  CAS  Google Scholar 

  164. Hanley PJ, Daut J (2005) K(ATP) channels and preconditioning: a re-examination of the role of mitochondrial K(ATP) channels and an overview of alternative mechanisms. J Mol Cell Cardiol 39:17–50

    Article  PubMed  CAS  Google Scholar 

  165. Halestrap AP, Clarke SJ, Javadov SA (2004) Mitochondrial permeability transition pore opening during myocardial reperfusion – a target for cardioprotection. Cardiovasc Res 61:372–385

    Article  PubMed  CAS  Google Scholar 

  166. Shanmuganathan S, Hausenloy DJ, Duchen MR, Yellon DM (2005) Mitochondrial permeability transition pore as a target for cardioprotection in the human heart. Am J Physiol Heart Circ Physiol 289:H237–H242

    Article  PubMed  CAS  Google Scholar 

  167. Thomson M (2002) Evidence of undiscovered cell regulatory mechanisms: phospho-proteins and protein kinases in mitochondria. Cell Mol Life Sci 59:213–219

    Article  PubMed  CAS  Google Scholar 

  168. Sugden MC, Orfali KA, Fryer LG, Holness MJ, Priestman DA (1997) Molecular mechanisms underlying the long-term impact of dietary fat to increase cardiac pyruvate dehydrogenase kinase: regulation by insulin, cyclic AMP and pyruvate. J Mol Cell Cardiol 29:1867–1875

    Article  PubMed  CAS  Google Scholar 

  169. Technikova-Dobrova Z, Sardanelli AM, Stanca MR, Papa S (1994) cAMP-dependent protein phosphorylation in mitochondria of bovine heart. FEBS Lett 350:187–191

    Article  PubMed  CAS  Google Scholar 

  170. Wang Y, Hirai K, Ashraf M (1999) Activation of mitochondrial ATP-sensitive K(+) channel for cardiac protection against ischemic injury is dependent on protein kinase C activity. Circ Res 85:731–741

    Article  PubMed  CAS  Google Scholar 

  171. Baines CP, Zhang J, Wang GW, Zheng YT, Xiu JX, Cardwell EM, Bolli R, Ping P (2002) Mitochondrial PKCepsilon and MAPK form signaling modules in the murine heart: enhanced mitochondrial PKCepsilon-MAPK interactions and differential MAPK activation in PKCepsilon-induced cardioprotection. Circ Res 90:390–397

    Article  PubMed  CAS  Google Scholar 

  172. Garlid KD, Costa AD, Cohen MV, Downey JM, Critz SD (2004) Cyclic GMP and PKG activate mito K(ATP) channels in isolated mitochondria. Cardiovasc J S Afr 15:S5

    Google Scholar 

  173. He H, Li HL, Lin A, Gottlieb RA (1999) Activation of the JNK pathway is important for cardiomyocyte death in response to simulated ischemia. Cell Death Differ 6:987–991

    Article  PubMed  CAS  Google Scholar 

  174. Aoki H, Kang PM, Hampe J, Yoshimura K, Noma T, Matsuzaki M, Izumo S (2002) Direct activation of mitochondrial apoptosis machinery by c-Jun N-terminal kinase in adult cardiac myocytes. J Biol Chem 277:10244–10250

    Article  PubMed  CAS  Google Scholar 

  175. Court NW, Kuo I, Quicley O, Bogoyevitch MA (2004) Phosphorylation of the mitochondrial protein Sab by stress-activated protein kinase 3. Biochem Biophys Res Commun 319:130–137

    Article  PubMed  CAS  Google Scholar 

  176. Baines CP, Song CX, Zheng YT, Wang GW, Zhang J, Wang OL, Guo Y, Bolli R, Cardwell EM, Ping P (2003) Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res 92:873–880

    Article  PubMed  CAS  Google Scholar 

  177. Lee I, Bender E, Kadenbach B (2002) Control of mitochondrial membrane potential and ROS formation by reversible phosphorylation of cytochrome c oxidase. Mol Cell Biochem 234–235:63–70

    Article  PubMed  Google Scholar 

  178. Schulenberg B, Aggeler R, Beechem JM, Capaldi RA, Patton WF (2003) Analysis of steady-state protein phosphorylation in mitochondria using a novel fluorescent phosphosensor dye. J Biol Chem 278:27251–27255

    Article  PubMed  CAS  Google Scholar 

  179. Hood DA, Joseph AM (2004) Mitochondrial assembly: protein import. Proc Nutr Soc 63:293–300

    Article  PubMed  CAS  Google Scholar 

  180. Colavecchia M, Christie LN, Kanwar YS, Hood DA (2003) Functional consequences of thyroid hormone-induced changes in the mitochondrial protein import pathway. Am J Physiol Endocrinol Metab 284:E29–E35

    PubMed  CAS  Google Scholar 

  181. Gibbs C (1999) Respiratory control in normal and hypertrophic hearts. Cardiovasc Res 42:567–570

    Article  PubMed  CAS  Google Scholar 

  182. McCormack JG, Halestrap AP, Denton RM (1990) Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev 70:391–425

    PubMed  CAS  Google Scholar 

  183. Harris DA, Das AM (1991) Control of mitochondrial ATP syn-thesis in heart. Biochem J 280:561–573

    PubMed  CAS  Google Scholar 

  184. Territo PR, Mootha VK, French SA, Balaban RS (2000) Ca2+ activation of heart mitochondrial phosphorylation: role of the F0/F1-ATPase. Am J Physiol Cell Physiol 278:C423–C435

    PubMed  CAS  Google Scholar 

  185. Takaki M, Zhao DD, Zhao LY, Araki J, Mori M, Suga H (1995) Suppression of myocardial mitochondrial respiratory function in acute failing hearts made by a short term Ca2+ free, high Ca2+ coronary perfusion. J Mol Cell Cardiol 27:2009–2013

    Article  PubMed  CAS  Google Scholar 

  186. He H, Chen M, Scheffler NK et al (2001) Phosphorylation of mitochondrial elongation factor Tu in ischemic myocardium: basis for chloramphenicol-mediated cardioprotection. Circ Res 89:461–467

    Article  PubMed  CAS  Google Scholar 

  187. Rutter GA, Rizzuto R (2000) Regulation of mitochondrial metabolism by ER Ca+ release:an intimate connection. Trends Biochem Sci 25:215–222

    Article  PubMed  CAS  Google Scholar 

  188. Duchen M (1999) Contributions of mitochondria to animal physiology: from homeostatic sensor to calcium signalling and cell death. J Physiol 516:1–17

    Article  PubMed  CAS  Google Scholar 

  189. Griffiths EJ (2000) Use of ruthenium red as an inhibitor of mitochondrial Ca(2+) uptake in single rat cardiomyocytes. FEBS Lett 486:257–260

    Article  PubMed  CAS  Google Scholar 

  190. Pacher P (2001) Hajnoczky G Propagation of the apoptotic signal by mitochondrial waves. EMBO J 20:4107–4121

    Article  PubMed  CAS  Google Scholar 

  191. Robb-Gaspers LD, Burnett P, Rutter GA et al (1998) Integrating cytosolic calcium signals into mitochondrial metabolic responses. EMBO J 17:4987–5000

    Article  PubMed  CAS  Google Scholar 

  192. Cortassa S, Aon MA, Marban E et al (2003) An integrated model of cardiac mitochondrial energy metabolism and calcium dynamics. Biophys J 84:2734–2755

    Article  PubMed  CAS  Google Scholar 

  193. Das AM, Harris DA (1991) Control of mitochondrial ATP synthase in rat cardiomyocytes: effects of thyroid hormone. Biochim Biophys Acta 1096:284–290

    Article  PubMed  CAS  Google Scholar 

  194. Rizzuto R (1998) Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca+ responses. Science 280:1763–1766

    Article  PubMed  CAS  Google Scholar 

  195. Csordas G, Thomas AP, Hajnoczky G (2001) Calcium signal transmission between ryanodine receptors and mitochondria in cardiac muscle. Trends Cardiovasc Med 11:269–275

    Article  PubMed  CAS  Google Scholar 

  196. Gunter TE, Gunter KK (2001) Uptake of calcium by mitochondria: transport and possible function. IUBMB Life 52:197–204

    Article  PubMed  CAS  Google Scholar 

  197. Buntinas L, Gunter KK, Sparagna GC et al (2001) The rapid mode of calcium uptake into heart mitochondria (RaM): comparison to RaM in liver mitochondria. Biochim Biophys Acta 1504:248–261

    Article  PubMed  CAS  Google Scholar 

  198. Crompton M, Costi A, Hayat L (1987) Evidence for the presence of a reversible Ca2+-dependent pore activated by oxidative stress in heart mitochondria. Biochem J 245:915–918

    PubMed  CAS  Google Scholar 

  199. Hajnoczky G, Csordas G, Yi M (2002) Old players in a new role: mitochondria-associated membranes, VDAC, and ryanodine receptors as contributors to calcium signal propagation from endoplasmic reticulum to the mitochondria. Cell Calcium 32:363–377

    Article  PubMed  CAS  Google Scholar 

  200. Oddis CV, Finkel MS (1995) Cytokine-stimulated nitric oxide production inhibits mitochondrial activity in cardiac myocytes. Biochem Biophys Res Commun 213:1002–1009

    Article  PubMed  CAS  Google Scholar 

  201. Zell R, Geck P, Werdan K et al (1997) TNF-alpha and IL-1 alpha inhibit both pyruvate dehydrogenase activity and mitochondrial function in cardiomyocytes: evidence for primary impairment of mitochondrial function. Mol Cell Biochem 177:61–67

    Article  PubMed  CAS  Google Scholar 

  202. Sammut IA, Harrison JC (2003) Cardiac mitochondrial complex activity is enhanced by heat shock proteins. Clin Exp Pharmacol Physiol 30:110–115

    Article  PubMed  CAS  Google Scholar 

  203. Bialik S, Cryns VL, Drincic A et al (1999) The mitochondrial apoptotic pathway is activated by serum and glucose deprivation in cardiac myocytes. Circ Res 85:403–414

    Article  PubMed  CAS  Google Scholar 

  204. Sparagna GC, Hickson-Bick DL, Buja LM et al (2001) Fatty acid-induced apoptosis in neonatal cardiomyocytes: redox signaling. Antioxid Redox Signal 3:71–79

    Article  PubMed  CAS  Google Scholar 

  205. Xia Y, Buja LM, Scarpulla RC, McMillin JB (1997). Electrical stimulation of neonatal cardio-myocytes results in sequential activation of nuclear genes governing mitochondrial proliferation and differentiation. Proc Natl Acad Sci USA 94:11399–11404

    Article  PubMed  CAS  Google Scholar 

  206. Riobo NA, Clementi E, Melani M et al (2001) Nitric oxide inhibits mitochondrial NADH:ubiquinone reductase activity through peroxynitrite formation. Biochem J 359:139–145

    Article  PubMed  CAS  Google Scholar 

  207. Poderoso JJ, Peralta JG, Lisdero CL et al (1998) Nitric oxide regulates oxygen uptake and hydrogen peroxide release by the isolated beating rat heart. Am J Physiol 274:C112–C119

    PubMed  CAS  Google Scholar 

  208. Wiesner RJ, Hornung TV, Garman JD et al (1999) Stimulation of mitochondrial gene expression and proliferation of mitochondria following impairment of cellular energy transfer by inhibition of phosphocreatine circuit in rat hearts. J Bioenerg Biomembr 31:559–567

    Article  PubMed  CAS  Google Scholar 

  209. Berridge MJ (2002) The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium 32:235–249

    Article  PubMed  CAS  Google Scholar 

  210. Kastan MB, Canman CE, Leonard CJ (1995) p53, cell cycle control and apoptosis: implications for cancer. Cancer Metastasis Rev 14:3–15

    Article  PubMed  CAS  Google Scholar 

  211. Agarwal ML, Taylor WR, Chernov MV, Chernova OB, Stark GR (1998) The p53 network. J Biol Chem 273:1–4

    Article  PubMed  CAS  Google Scholar 

  212. Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP (1996) Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274:948–953

    Article  PubMed  CAS  Google Scholar 

  213. Thut CJ, Goodrich JA, Tjian R (1997) Repression of p53-mediated transcription by MDM2: a dual mechanism. Genes Dev 11:1974–1986

    Article  PubMed  CAS  Google Scholar 

  214. Moll UM, Zaika A (2001) Nuclear and mitochondrial apoptosis pathways of p53. FEBS Lett 493:65–69

    Article  PubMed  CAS  Google Scholar 

  215. Moll UM, Marchenko N, Zhang XK (2006) p53 and Nur77/TR3 – transcription factors that directly target mitochondria for cell death induction. Oncogene 25:4725–4743

    Article  PubMed  CAS  Google Scholar 

  216. Pierzchalski P, Reiss K, Cheng W, Cirielli C, Kajstura J, Nitahara JA, Rizk M, Capogrossi MC, Anversa P (1997) p53 Induces myocyte apoptosis via the activation of the renin-angiotensin system. Exp Cell Res 234:57–65

    Article  PubMed  CAS  Google Scholar 

  217. Long X, Crow MT, Sollott SJ, O’Neil L, Menees DS, Hipolito ML, Boluyt MO, Asai T, Lakatta EG (1998) Enhanced expression of p53 and apoptosis induced by blockade of the vacuolar proton ATPase in cardiomyotes. J Clin Invest 101:1453–1461

    Article  PubMed  CAS  Google Scholar 

  218. Leri A, Claudio PP, Li Q, Wang X, Reiss K, Wang S, Malhotra A, Kajstura J, Anversa P (1998) Stretch-mediated release of angiotensin II induces myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the Bcl-2-to-Bax protein ratio in the cell. J Clin Invest 101:1326–1342

    Article  PubMed  CAS  Google Scholar 

  219. Liu G, Chen X (2006) Regulation of the p53 transcriptional activity. J Cell Biochem 97:448–458

    Article  PubMed  CAS  Google Scholar 

  220. Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303:1010–1014

    Article  PubMed  CAS  Google Scholar 

  221. Steegenga WT, van der Eb AJ, Jochemsen AG (1996) How phosphorylation regulates the activity of p53. J Mol Biol 263:103–113

    Article  PubMed  CAS  Google Scholar 

  222. Giaccia AJ, Kastan MB (1998) The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev 12:2973–2983

    Article  PubMed  CAS  Google Scholar 

  223. Huang C, Ma WY, Maxiner A, Sun Y, Dong Z (1999) p38 kinase mediates UV-induced phosphorylation of p53 protein at serine 389. J Biol Chem 274:12229–12235

    Article  PubMed  CAS  Google Scholar 

  224. Takenaka I, Morin F, Seizinger BR, Kley N (1995) Regulation of the sequence-specific DNA binding function of p53 by protein kinase C and protein phosphatases. J Biol Chem 270:5405–5411

    Article  PubMed  CAS  Google Scholar 

  225. Meek DW, Simon S, Kikkawa U, Eckhart W (1990) The p53 tumor suppressor protein is phosphorylated at serine 389 by casein kinase II. EMBO J 9:3253–3260

    PubMed  CAS  Google Scholar 

  226. Lees-Miller SP, Sakaguchi K, Ullrich SJ, Appella E, Anderson CW (1992) Human DNA-activated protein kinase phosphorylates serine 15 and 37 in the amino-terminal transactivation domain of human p53. Mol Cell Biol 12:5041–5049

    PubMed  CAS  Google Scholar 

  227. Banin S, Moyal L, Shieh S-Y, Taya Y, Anderson CW, Chessa L, Smorodinsky NI, Prives C, Reiss Y, Shiloh Y, Ziv Y (1998) Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281:1674–1677

    Article  PubMed  CAS  Google Scholar 

  228. Canman CE, Lim D-S, Cimprich KA, Taya Y, Tamai K, Sakaguchi K, Appella E, Kastan MB, Siliciano JD (1998) Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science 281:1677–1679

    Article  PubMed  CAS  Google Scholar 

  229. Tibbetts RS, Brumbaugh KM, Williams JM, Sarkaria JN, Cliby WA, Shieh S-Y, Taya Y, Prives C, Abraham RT (1999) A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev 13:152–157

    Article  PubMed  CAS  Google Scholar 

  230. Shieh S-Y, Ikeda M, Taya Y, Prives C (1997) DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 91:325–334

    Article  PubMed  CAS  Google Scholar 

  231. Lambert PF, Kashanchi F, Radonovich MF, Shiekhattar R, Brady JN (1998) Phosphorylation of p53 serine 15 increases interaction with CBP. J Biol Chem 273:33048–33053

    Article  PubMed  CAS  Google Scholar 

  232. McNeill-Blue C, Wetmore BA, Sanchez JF, Freed WJ, Alex Merrick B (2006) Apoptosis mediated by p53 in rat neural AF5 cells following treatment with hydrogen peroxide and staurosporine. Brain Res 1112:1–15

    Article  PubMed  CAS  Google Scholar 

  233. von Harsdorf R, Li PF, Dietz R (1999) Signaling pathways in reactive oxygen species-induced cardiomyocyte apoptosis. Circulation 99:2934–2941

    Article  Google Scholar 

  234. Long X, Goldenthal MJ, Wu GM, Marin-Garcia J (2004) Mitochondrial Ca2+ flux and respiratory enzyme activity decline are early events in cardiomyocyte response to H2O2. J Mol Cell Cardiol 37:63–70

    Article  PubMed  CAS  Google Scholar 

  235. Chandel NS, Vander Heiden MG, Thompson CB, Schumacker P (2000) Redox regulation of p53 during hypoxia. Oncogene 19:3840–3848

    Article  PubMed  CAS  Google Scholar 

  236. Ashcroft M, Kubbutat MH, Vousden KH (1999) Regulation of p53 function and stability by phosphorylation. Mol Cell Biol 19:1751–1758

    PubMed  CAS  Google Scholar 

  237. Unger T, Sionov RV, Moallem E, Yee CL, Howley PM, Oren M, Haupt Y (1999) Mutations in serines 15 and 20 of human p53 impair its apoptotic activity. Oncogene 18:3205–3212

    Article  PubMed  CAS  Google Scholar 

  238. Siliciano JD, Canman CE, Taya Y, Sakaguchi K, Appella E, Kastan MB (1997) DNA damage induces phosphorylation of the amino terminus of p53. Genes Dev 11:3471–3481

    Article  PubMed  CAS  Google Scholar 

  239. Sheikh MS, Hollander MC, Fornance AJ (2000) Role of Gadd45 in apoptosis. Biochem Pharmacol 59:43–45

    Article  PubMed  CAS  Google Scholar 

  240. She QB, Chen N, Dong Z (2000) ERKs and p38 kinase phosphorylate p53 protein at serine 15 in response to UV radiation. J Biol Chem 275:20444–20449

    Article  PubMed  CAS  Google Scholar 

  241. Chen K, Albano A, Ho A, Keaney JF (2003) Activation of p53 by oxidative stress involves platelet-derived growth factor-beta receptor-mediated ataxia telangiectasia mutated (ATM) kinase activation. J Biol Chem 278:39527–39533

    Article  PubMed  CAS  Google Scholar 

  242. Karin M, Hunter T (1995) Transcriptional control by protein phosphorylation: signal transmission from the cell surface to the nucleus. Curr Biol 5:747–757

    Article  PubMed  CAS  Google Scholar 

  243. Hunter T (1995) Protein kinases and phosphatases: the yin and yang of protein phosphorylation and signaling. Cell 80:225–236

    Article  PubMed  CAS  Google Scholar 

  244. Guyton KZ, Liu Y, Gorospe M, Xu Q, Holbrook NJ (1996) Activation of mitogen-activated protein kinase by H2O2. Role in cell survival following oxidant injury. J Biol Chem 271:4138–4142

    Article  PubMed  CAS  Google Scholar 

  245. Treisman R (1996) Regulation of transcription by MAP kinase cascades. Curr Opin Cell Biol 8:205–215

    Article  PubMed  CAS  Google Scholar 

  246. Cobb MH, Goldsmith EJ (1995) How MAP kinases are regulated. J Biol Chem 270:14843–14846

    Article  PubMed  CAS  Google Scholar 

  247. Bulavin DV, Saito S, Hollander MC, Sakaguchi K, Anderson CW, Appella E, Fornace AJ (1999) Phosphorylation of human p53 by p38 kinase coordinates N-terminal phosphorylation and apoptosis in response to UV radiation. EMBO J 18:6845–6854

    Article  PubMed  CAS  Google Scholar 

  248. Jackson SP (1997) DNA-dependent protein kinase. Int J Biochem Cell Biol 29:935–938

    Article  PubMed  CAS  Google Scholar 

  249. Keith CT, Schreiber SL (1995) PIK-related kinases: DNA repair, recombination, and cell cycle checkpoints. Science 270:50–51

    Article  PubMed  CAS  Google Scholar 

  250. Jimenez GS, Bryntesson F, Torres-Arzayus MI et al (1999) DNA-dependent protein kinase is not required for the p53-dependent response to DNA damage. Nature 400:81–83

    Article  PubMed  CAS  Google Scholar 

  251. Zhan Q, Carrier F, Fornace AJ (1993) Induction of cellular p53 activity by DNA-damaging agents and growth arrest. Mol Cell Biol 13:4242–4250

    PubMed  CAS  Google Scholar 

  252. Toth A, Jeffers JR, Nickson P, Min JY, Morgan JP, Zambetti GP, Erhardt P (2006) Targeted deletion of Puma attenuates cardiomyocyte death and improves cardiac function during ischemia-reperfusion. Am J Physiol Heart Circ Physiol 291:H52–H60

    Article  PubMed  CAS  Google Scholar 

  253. Kemp TJ, Causton HC, Clerk A (2003) Changes in gene expression induced by H2O2 in cardiac myocytes. Biochem Biophys Res Commun 307:416–421

    Article  PubMed  CAS  Google Scholar 

  254. Shohet RV, Garcia JA (2007) Keeping the engine primed: HIF factors as key regulators of cardiac metabolism and angiogenesis during ischemia. J Mol Med 85:1309–1315

    Article  PubMed  Google Scholar 

  255. Sano M, Komuro I (2008) P53 and its role in the development of heart failure. Nippon Rinsho 66:1013–1021

    PubMed  Google Scholar 

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    José Marín-García MD (Director)

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Marín-García, J. (2010). Signaling Cascades in Heart Failure: From Cardiomyocytes Growth and Survival to Mitochondrial Signaling Pathways. In: Heart Failure. Contemporary Cardiology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-147-9_7

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