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Cardiology Research and Practice
Volume 2011, Article ID 972807, 15 pages
http://dx.doi.org/10.4061/2011/972807
Review Article

Molecular Mechanisms in Exercise-Induced Cardioprotection

Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada V6T 1Z3

Received 26 September 2010; Revised 16 December 2010; Accepted 3 January 2011

Academic Editor: Christina Chrysohoou

Copyright © 2011 Saeid Golbidi and Ismail Laher. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. F. Sofi, A. Capalbo, F. Cesari, R. Abbate, and G. F. Gensini, “Physical activity during leisure time and primary prevention of coronary heart disease: an updated meta-analysis of cohort studies,” European Journal of Cardiovascular Prevention and Rehabilitation, vol. 15, no. 3, pp. 247–257, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. J. A. Berlin and G. A. Colditz, “A meta-analysis of physical activity in the prevention of coronary heart disease,” American Journal of Epidemiology, vol. 132, no. 4, pp. 612–628, 1990. View at Google Scholar · View at Scopus
  3. M. Nocon, T. Hiemann, F. Müller-Riemenschneider, F. Thalau, S. Roll, and S. N. Willich, “Association of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis,” European Journal of Cardiovascular Prevention and Rehabilitation, vol. 15, no. 3, pp. 239–246, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. J. Myers, M. Prakash, V. Froelicher, D. Do, S. Partington, and J. Edwin Atwood, “Exercise capacity and mortality among men referred for exercise testing,” The New England Journal of Medicine, vol. 346, no. 11, pp. 793–801, 2002. View at Publisher · View at Google Scholar · View at Scopus
  5. P. Kokkinos, J. Myers, C. Faselis et al., “Exercise capacity and mortality in older men: a 20-year follow-up study,” Circulation, vol. 122, no. 8, pp. 790–797, 2010. View at Publisher · View at Google Scholar
  6. P. Kokkinos, M. Doumas, J. Myers et al., “A graded association of exercise capacity and all-cause mortality in males with high-normal blood pressure,” Blood Pressure, vol. 18, no. 5, pp. 261–267, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. S. Ghosh, S. Golbidi, I. Werner, B. C. Verchere, and I. Laher, “Selecting exercise regimens and strains to modify obesity and diabetes in rodents: an overview,” Clinical Science, vol. 119, no. 2, pp. 57–74, 2010. View at Publisher · View at Google Scholar
  8. N. Yamashita, S. Hoshida, K. Otsu, M. Asahi, T. Kuzuya, and M. Hori, “Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation,” Journal of Experimental Medicine, vol. 189, no. 11, pp. 1699–1706, 1999. View at Publisher · View at Google Scholar · View at Scopus
  9. S. L. Lennon, J. C. Quindry, K. L. Hamilton et al., “Elevated MnSOD is not required for exercise-induced cardioprotection against myocardial stunning,” American Journal of Physiology, vol. 287, no. 2, pp. H975–H980, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. S. L. Lennon, J. Quindry, K. L. Hamilton et al., “Loss of exercise-induced cardioprotection after cessation of exercise,” Journal of Applied Physiology, vol. 96, no. 4, pp. 1299–1305, 2004. View at Publisher · View at Google Scholar · View at Scopus
  11. Z. Paroo, J. V. Haist, M. Karmazyn, and E. G. Noble, “Exercise improves postischemic cardiac function in males but not females: consequences of a novel sex-specific heat shock protein 70 response,” Circulation Research, vol. 90, no. 8, pp. 911–917, 2002. View at Publisher · View at Google Scholar · View at Scopus
  12. H. Selye, “A syndrome produced by diverse nocuous agents,” Journal of Neuropsychiatry and Clinical Neurosciences, vol. 10, no. 2, pp. 230–231, 1998. View at Google Scholar · View at Scopus
  13. M. S. Marber, R. Mestril, S. H. Chi, M. R. Sayen, D. M. Yellon, and W. H. Dillmann, “Overexpression of the rat inducible 70-kD heat stress protein in a transgenic mouse increases the resistance of the heart to ischemic injury,” Journal of Clinical Investigation, vol. 95, no. 4, pp. 1446–1456, 1995. View at Google Scholar · View at Scopus
  14. S. D. Guttman, C. V. C. Glover, C. D. Allis, and M. A. Gorovsky, “Heat shock, deciliation and release from anoxia induce the synthesis of the same set of polypeptides in starved T. pyriformis,” Cell, vol. 22, no. 1, pp. 299–307, 1980. View at Google Scholar · View at Scopus
  15. G. Weitzel, U. Pilatus, and L. Rensing, “Similar dose response of heat shock protein synthesis and intracellular pH change in yeast,” Experimental Cell Research, vol. 159, no. 1, pp. 252–256, 1985. View at Google Scholar · View at Scopus
  16. C. Adrie, C. Richter, M. Bachelet et al., “Contrasting effects of NO and peroxynitrites on HSP70 expression and apoptosis in human monocytes,” American Journal of Physiology, vol. 279, no. 2, pp. C452–C460, 2000. View at Google Scholar · View at Scopus
  17. H. L. Chiang, S. R. Terlecky, C. P. Plant, and J. F. Dice, “A role for a 70-kilodaton heat shock protein in lysosomal degradation of intracellular proteins,” Science, vol. 246, no. 4928, pp. 382–385, 1989. View at Google Scholar · View at Scopus
  18. W. J. Welch, J. I. Garrels, G. P. Thomas, J. J. Lin, and J. R. Feramisco, “Biochemical characterization of the mammalian stress proteins and identification of two stress proteins as glucose- and Ca2+-ionophore-regulated proteins,” The Journal of Biological Chemistry, vol. 258, no. 11, pp. 7102–7111, 1983. View at Google Scholar · View at Scopus
  19. J. J. Sciandra and J. R. Subjeck, “The effects of glucose on protein synthesis and thermosensitivity in Chinese hamster ovary cells,” The Journal of Biological Chemistry, vol. 258, no. 20, pp. 12091–12093, 1983. View at Google Scholar · View at Scopus
  20. M. Locke, “The cellular stress response to exercise: role of stress proteins,” Exercise and Sport Sciences Reviews, vol. 25, pp. 105–136, 1997. View at Google Scholar · View at Scopus
  21. M. Locke, E. G. Noble, R. M. Tanguay, M. R. Feild, S. E. Ianuzzo, and C. D. Ianuzzo, “Activation of heat-shock transcription factor in rat heart after heat shock and exercise,” American Journal of Physiology, vol. 268, no. 6, pp. C1387–C1394, 1995. View at Google Scholar · View at Scopus
  22. S. K. Powers, M. Locke, and H. A. Demirel, “Exercise, heat shock proteins, and myocardial protection from I-R injury,” Medicine and Science in Sports and Exercise, vol. 33, no. 3, pp. 386–392, 2001. View at Google Scholar · View at Scopus
  23. D. S. Latchman, “Heat shock proteins and cardiac protection,” Cardiovascular Research, vol. 51, no. 4, pp. 637–646, 2001. View at Publisher · View at Google Scholar · View at Scopus
  24. I. A. Sammut and J. C. Harrison, “Cardiac mitochondrial complex activity is enhanced by heat shock proteins,” Clinical and Experimental Pharmacology and Physiology, vol. 30, no. 1-2, pp. 110–115, 2003. View at Publisher · View at Google Scholar · View at Scopus
  25. J. Jayakumar, K. Suzuki, I. A. Sammut et al., “Heat shock protein 70 gene transfection protects mitochondrial and ventricular function against ischemia-reperfusion injury,” Circulation, vol. 104, no. 1, pp. i303–i307, 2001. View at Google Scholar · View at Scopus
  26. Z. Paroo, M. J. Meredith, M. Locke, J. V. Haist, M. Karmazyn, and E. G. Noble, “Redox signaling of cardiac HSF1 DNA binding,” American Journal of Physiology, vol. 283, no. 2, pp. C404–C411, 2002. View at Google Scholar · View at Scopus
  27. C. W. Melling, D. B. Thorp, and E. G. Noble, “Regulation of myocardial heat shock protein 70 gene expression following exercise,” Journal of Molecular and Cellular Cardiology, vol. 37, no. 4, pp. 847–855, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. C. W. J. Melling, D. B. Thorp, K. J. Milne, M. P. Krause, and E. G. Noble, “Exercise-mediated regulation of Hsp70 expression following aerobic exercise training,” American Journal of Physiology, vol. 293, no. 6, pp. H3692–H3698, 2007. View at Publisher · View at Google Scholar · View at Scopus
  29. K. Suzuki, B. Murtuza, I. A. Sammut et al., “Heat shock protein 72 enhances manganese superoxide dismutase activity during myocardial ischemia-reperfusion injury, associated with mitochondrial protection and apoptosis reduction,” Circulation, vol. 106, no. 13, pp. I270–I276, 2002. View at Google Scholar · View at Scopus
  30. J. Jayakumar, K. Suzuki, I. A. Sammut et al., “Heat shock protein 70 gene transfection protects mitochondrial and ventricular function against ischemia-reperfusion injury,” Circulation, vol. 104, no. 12, supplement, pp. I303–i307, 2001. View at Google Scholar · View at Scopus
  31. R. Steel, J. P. Doherty, K. Buzzard, N. Clemons, C. J. Hawkins, and R. L. Anderson, “Hsp72 inhibits apoptosis upstream of the mitochondria and not through interactions with Apaf-1,” The Journal of Biological Chemistry, vol. 279, no. 49, pp. 51490–51499, 2004. View at Publisher · View at Google Scholar · View at Scopus
  32. I. J. Benjamin and D. R. McMillan, “Stress (heat shock) proteins molecular chaperones in cardiovascular biology and disease,” Circulation Research, vol. 83, no. 2, pp. 117–132, 1998. View at Google Scholar · View at Scopus
  33. R. P. Taylor, M. B. Harris, and J. W. Starnes, “Acute exercise can improve cardioprotection without increasing heat shock protein content,” American Journal of Physiology, vol. 276, no. 3, pp. H1098–H1102, 1999. View at Google Scholar · View at Scopus
  34. K. L. Hamilton, S. K. Powers, T. Sugiura et al., “Short-term exercise training can improve myocardial tolerance to I/R without elevation in heat shock proteins,” American Journal of Physiology, vol. 281, no. 3, pp. H1346–H1352, 2001. View at Google Scholar · View at Scopus
  35. J. C. Quindry, K. L. Hamilton, J. P. French et al., “Exercise-induced HSP-72 elevation and cardioprotection against infarct and apoptosis,” Journal of Applied Physiology, vol. 103, no. 3, pp. 1056–1062, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. J. C. Quindry, K. L. Hamilton, J. P. French et al., “Heat shock protein 72 expression is not essential for exercise induced protection against infarction and apoptosis following ischemia reperfusion,” The FASEB Journal, vol. 20, no. 4, A318 pages, 2006. View at Google Scholar
  37. D. Whitley, S. P. Goldberg, and W. D. Jordan, “Heat shock proteins: a review of the molecular chaperones,” Journal of Vascular Surgery, vol. 29, no. 4, pp. 748–751, 1999. View at Google Scholar · View at Scopus
  38. S. Golbidi and I. Laher, “Antioxidant therapy in human endocrine disorders,” Medical Science Monitor, vol. 16, no. 1, pp. RA9–RA24, 2010. View at Google Scholar · View at Scopus
  39. A. G. Cox, C. C. Winterbourn, and M. B. Hampton, “Mitochondrial peroxiredoxin involvement in antioxidant defence and redox signalling,” Biochemical Journal, vol. 425, no. 2, pp. 313–325, 2010. View at Publisher · View at Google Scholar · View at Scopus
  40. F. Gündüz, U. K. Sentürk, O. Kuru, B. Aktekin, and M. R. Aktekin, “The effect of one year's swimming exercise on oxidant stress and antioxidant capacity in aged rats,” Physiological Research, vol. 53, no. 2, pp. 171–176, 2004. View at Google Scholar · View at Scopus
  41. K. Husain and S. M. Somani, “Interaction of exercise and adenosine receptor agonist and antagonist on rat heart antioxidant defense system,” Molecular and Cellular Biochemistry, vol. 270, no. 1-2, pp. 209–214, 2005. View at Publisher · View at Google Scholar · View at Scopus
  42. K. L. Hamilton, J. L. Staib, T. Phillips, A. Hess, S. L. Lennon, and S. K. Powers, “Exercise, antioxidants, and HSP72: protection against myocardial ischemia/reperfusion,” Free Radical Biology and Medicine, vol. 34, no. 7, pp. 800–809, 2003. View at Publisher · View at Google Scholar · View at Scopus
  43. H. A. Demirel, S. K. Powers, M. A. Zergeroglu et al., “Short-term exercise improves myocardial tolerance to in vivo ischemia-reperfusion in the rat,” Journal of Applied Physiology, vol. 91, no. 5, pp. 2205–2212, 2001. View at Google Scholar · View at Scopus
  44. S. L. Lennon, J. Quindry, K. L. Hamilton et al., “Loss of exercise-induced cardioprotection after cessation of exercise,” Journal of Applied Physiology, vol. 96, no. 4, pp. 1299–1305, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. J. W. Starnes, R. P. Taylor, and Y. Park, “Exercise improves postischemic function in aging hearts,” American Journal of Physiology, vol. 285, no. 1, pp. H347–H351, 2003. View at Google Scholar · View at Scopus
  46. N. Yamashita, S. Hoshida, K. Otsu, M. Asahi, T. Kuzuya, and M. Hori, “Exercise provides direct biphasic cardioprotection via manganese superoxide dismutase activation,” Journal of Experimental Medicine, vol. 189, no. 11, pp. 1699–1706, 1999. View at Publisher · View at Google Scholar · View at Scopus
  47. D. A. Brown, K. N. Jew, G. C. Sparagna, T. I. Musch, and R. L. Moore, “Exercise training preserves coronary flow and reduces infarct size after ischemia-reperfusion in rat heart,” Journal of Applied Physiology, vol. 95, no. 6, pp. 2510–2518, 2003. View at Google Scholar · View at Scopus
  48. J. P. French, K. L. Hamilton, J. C. Quindry, Y. Lee, P. A. Upchurch, and S. K. Powers, “Exercise-induced protection against myocardial apoptosis and necrosis: MnSOD, calcium-handling proteins, and calpain,” FASEB Journal, vol. 22, no. 8, pp. 2862–2871, 2008. View at Publisher · View at Google Scholar · View at Scopus
  49. K. L. Hamilton, J. C. Quindry, J. P. French et al., “MnSOD antisense treatment and exercise-induced protection against arrhythmias,” Free Radical Biology and Medicine, vol. 37, no. 9, pp. 1360–1368, 2004. View at Publisher · View at Google Scholar · View at Scopus
  50. S. L. Lennon, J. C. Quindry, K. L. Hamilton et al., “Elevated MnSOD is not required for exercise-induced cardioprotection against myocardial stunning,” American Journal of Physiology, vol. 287, no. 2, pp. H975–H980, 2004. View at Publisher · View at Google Scholar · View at Scopus
  51. A. N. Kavazis, “Exercise preconditioning of the myocardium,” Sports Medicine, vol. 39, no. 11, pp. 923–935, 2009. View at Publisher · View at Google Scholar · View at Scopus
  52. S. K. Powers, J. C. Quindry, and A. N. Kavazis, “Exercise-induced cardioprotection against myocardial ischemia-reperfusion injury,” Free Radical Biology and Medicine, vol. 44, no. 2, pp. 193–201, 2008. View at Publisher · View at Google Scholar · View at Scopus
  53. F. P. Leung, L. M. Yung, I. Laher, X. Yao, Z. Y. Chen, and YU. Huang, “Exercise, vascular wall and cardiovascular diseases: an update (part 1),” Sports Medicine, vol. 38, no. 12, pp. 1009–1024, 2008. View at Google Scholar · View at Scopus
  54. J. Rehman, J. Li, L. Parvathaneni et al., “Exercise acutely increases circulating endothelial progenitor cells and monocyte-/macrophage-derived angiogenic cells,” Journal of the American College of Cardiology, vol. 43, no. 12, pp. 2314–2318, 2004. View at Publisher · View at Google Scholar · View at Scopus
  55. S. Steiner, A. Niessner, S. Ziegler et al., “Endurance training increases the number of endothelial progenitor cells in patients with cardiovascular risk and coronary artery disease,” Atherosclerosis, vol. 181, no. 2, pp. 305–310, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. U. Laufs, A. Urhausen, N. Werner et al., “Running exercise of different duration and intensity: effect on endothelial progenitor cells in healthy subjects,” European Journal of Cardiovascular Prevention and Rehabilitation, vol. 12, no. 4, pp. 407–414, 2005. View at Publisher · View at Google Scholar · View at Scopus
  57. M. S. O'Reilly, T. Boehm, Y. Shing et al., “Endostatin: an endogenous inhibitor of angiogenesis and tumor growth,” Cell, vol. 88, no. 2, pp. 277–285, 1997. View at Publisher · View at Google Scholar · View at Scopus
  58. J. Obeso, J. Weber, and R. Auerbach, “A hemangioendothelioma-derived cell line: its use as a model for the study of endothelial cell biology,” Laboratory Investigation, vol. 63, no. 2, pp. 259–269, 1990. View at Google Scholar · View at Scopus
  59. M. Ferreras, U. Felbor, T. Lenhard, B. R. Olsen, and J. M. Delaissé, “Generation and degradation of human endostatin proteins by various proteinases,” FEBS Letters, vol. 486, no. 3, pp. 247–251, 2000. View at Publisher · View at Google Scholar · View at Scopus
  60. J. Saarela, M. Rehn, A. Oikarinen, H. Autio-Harmainen, and T. Pihlajaniemi, “The short and long forms of type XVIII collagen show clear tissue specificities in their expression and location in basement membrane zones in humans,” American Journal of Pathology, vol. 153, no. 2, pp. 611–626, 1998. View at Google Scholar · View at Scopus
  61. M. Shichiri and Y. Hirata, “Antiangiogenesis signals by endostatin,” FASEB Journal, vol. 15, no. 6, pp. 1044–1053, 2001. View at Publisher · View at Google Scholar · View at Scopus
  62. L. Taddei, P. Chiarugi, L. Brogelli et al., “Inhibitory effect of full-length human endostatin on in vitro angiogenesis,” Biochemical and Biophysical Research Communications, vol. 263, no. 2, pp. 340–345, 1999. View at Publisher · View at Google Scholar · View at Scopus
  63. K. Eriksson, P. Magnusson, J. Dixelius, L. Claesson-Welsh, and M. J. Cross, “Angiostatin and endostatin inhibit endothelial cell migration in response to FGF and VEGF without interfering with specific intracellular signal transduction pathways,” FEBS Letters, vol. 536, no. 1–3, pp. 19–24, 2003. View at Publisher · View at Google Scholar · View at Scopus
  64. J. M. Isner and D. W. Losordo, “Therapeutic angiogenesis for heart failure,” Nature Medicine, vol. 5, no. 5, pp. 491–492, 1999. View at Publisher · View at Google Scholar · View at Scopus
  65. F. L. Celletti, P. R. Hilfiker, P. Ghafouri, and M. D. Dake, “Effect of human recombinant vascular endothelial growth factor on progression of atherosclerotic plaque,” Journal of the American College of Cardiology, vol. 37, no. 8, pp. 2126–2130, 2001. View at Publisher · View at Google Scholar · View at Scopus
  66. K. B. Lemström, R. Krebs, A. I. Nykänen et al., “Vascular endothelial growth factor enhances cardiac allograft arteriosclerosis,” Circulation, vol. 105, no. 21, pp. 2524–2530, 2002. View at Publisher · View at Google Scholar · View at Scopus
  67. R. S. Richardson, H. Wagner, S. R. D. Mudaliar, E. Saucedo, R. Henry, and P. D. Wagner, “Exercise adaptation attenuates VEGF gene expression in human skeletal muscle,” American Journal of Physiology, vol. 279, no. 2, pp. H772–H778, 2000. View at Google Scholar · View at Scopus
  68. J. W. Gu, G. Gadonski, J. Wang, I. Makey, and T. H. Adair, “Exercise increases endostatin in circulation of healthy volunteers,” BMC Physiology, vol. 4, article 1, pp. 1–6, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. K. Brixius, S. Schoenberger, D. Ladage et al., “Long-term endurance exercise decreases antiangiogenic endostatin signalling in overweight men aged 50–60 years,” British Journal of Sports Medicine, vol. 42, no. 2, pp. 126–129, 2008. View at Publisher · View at Google Scholar · View at Scopus
  70. M. D. Brown, “Exercise and coronary vascular remodelling in the healthy heart,” Experimental Physiology, vol. 88, no. 5, pp. 645–658, 2003. View at Publisher · View at Google Scholar · View at Scopus
  71. W. L. Haskell, C. Sims, J. Myll, W. M. Bortz, F. G. St. Goar F.G., and E. L. Alderman, “Coronary artery size and dilating capacity in ultradistance runners,” Circulation, vol. 87, no. 4, pp. 1076–1082, 1993. View at Google Scholar · View at Scopus
  72. H. L. Wyatt and J. Mitchell, “Influences of physical conditioning and deconditioning on coronary vasculature of dogs,” Journal of Applied Physiology, vol. 45, no. 4, pp. 619–625, 1978. View at Google Scholar · View at Scopus
  73. R. Belardinelli, D. Georgiou, L. Ginzton, G. Cianci, and A. Purcaro, “Effects of moderate exercise training on thallium uptake and contractile response to low-dose dobutamine of dysfunctional myocardium in patients with ischemic cardiomyopathy,” Circulation, vol. 97, no. 6, pp. 553–561, 1998. View at Google Scholar · View at Scopus
  74. D. N. Sim and W. A. Neill, “Investigation of the physiological basis for increased exercise threshold for angina pectoris after physical conditioning,” Journal of Clinical Investigation, vol. 54, no. 3, pp. 763–770, 1974. View at Google Scholar · View at Scopus
  75. M. V. Cohen, C. P. Baines, and J. M. Downey, “Ischemic preconditioning: from adenosine receptor to K(ATP) channel,” Annual Review of Physiology, vol. 62, pp. 79–109, 2000. View at Publisher · View at Google Scholar · View at Scopus
  76. R. Bolli, “The late phase of preconditioning,” Circulation Research, vol. 87, no. 11, pp. 972–983, 2000. View at Google Scholar · View at Scopus
  77. H. A. Demirel, S. K. Powers, C. Caillaud et al., “Exercise training reduces myocardial lipid peroxidation following short- term ischemia-reperfusion,” Medicine and Science in Sports and Exercise, vol. 30, no. 8, pp. 1211–1216, 1998. View at Publisher · View at Google Scholar · View at Scopus
  78. H. A. Demirel, S. K. Powers, M. A. Zergeroglu et al., “Short-term exercise improves myocardial tolerance to in vivo ischemia-reperfusion in the rat,” Journal of Applied Physiology, vol. 91, no. 5, pp. 2205–2212, 2001. View at Google Scholar · View at Scopus
  79. R. Bolli, “Preconditioning: a paradigm shift in the biology of myocardial ischemia,” American Journal of Physiology, vol. 292, no. 1, pp. H19–H27, 2007. View at Publisher · View at Google Scholar · View at Scopus
  80. S. Hoshida, N. Yamashita, K. Otsu, and M. Hori, “Repeated physiologic stresses provide persistent cardioprotection against ischemia-reperfusion injury in rats,” Journal of the American College of Cardiology, vol. 40, no. 4, pp. 826–831, 2002. View at Publisher · View at Google Scholar · View at Scopus
  81. O. Nagy, A. Hajnal, J. R. Parratt, and A. Végh, “Delayed exercise-induced protection against arrhythmias in dogs—effect of celecoxib,” European Journal of Pharmacology, vol. 499, no. 1-2, pp. 197–199, 2004. View at Publisher · View at Google Scholar · View at Scopus
  82. J. C. Quindry, J. French, K. L. Hamilton, Y. Lee, J. Selsby, and S. K. Powers, “Cyclooxygenase 2 is unaltered by exercise in the young and old heart,” Medicine & Science in Sports & Exercise, vol. 38, p. s416, 2006. View at Google Scholar
  83. J. C. Quindry, J. French, K. L. Hamilton, Y. Lee, J. Selsby, and S. Powers, “Exercise does not increase cyclooxygenase-2 myocardial levels in young or senescent hearts,” Journal of Physiological Sciences, vol. 60, no. 3, pp. 181–186, 2010. View at Publisher · View at Google Scholar · View at Scopus
  84. S. E. Logue, A. B. Gustafsson, A. Samali, and R. A. Gottlieb, “Ischemia/reperfusion injury at the intersection with cell death,” Journal of Molecular and Cellular Cardiology, vol. 38, no. 1, pp. 21–33, 2005. View at Publisher · View at Google Scholar · View at Scopus
  85. J. Wu and R. J. Kaufman, “From acute ER stress to physiological roles of the unfolded protein response,” Cell Death and Differentiation, vol. 13, no. 3, pp. 374–384, 2006. View at Publisher · View at Google Scholar · View at Scopus
  86. M. Vitadello, D. Penzo, V. Petronilli et al., “Overexpression of the stress protein Grp94 reduces cardiomyocyte necrosis due to calcium overload and simulated ischemia,” The FASEB Journal, vol. 17, no. 8, pp. 923–925, 2003. View at Google Scholar · View at Scopus
  87. J. J. Martindale, R. Fernandez, D. Thuerauf et al., “Endoplasmic reticulum stress gene induction and protection from ischemia/reperfusion injury in the hearts of transgenic mice with a tamoxifen-regulated form of ATF6,” Circulation Research, vol. 98, no. 9, pp. 1186–1193, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. Z. Murlasits, Y. Lee, and S. K. Powers, “Short-term exercise does not increase ER stress protein expression in cardiac muscle,” Medicine and Science in Sports and Exercise, vol. 39, no. 9, pp. 1522–1528, 2007. View at Publisher · View at Google Scholar · View at Scopus
  89. A. B. Stein, X. L. Tang, Y. Guo, YU. T. Xuan, B. Dawn, and R. Bolli, “Delayed adaptation of the heart to stress: late preconditioning,” Stroke, vol. 35, no. 11, pp. 2676–2679, 2004. View at Publisher · View at Google Scholar · View at Scopus
  90. P. F. Méry, C. Pavoine, L. Belhassen, F. Pecker, and R. Fischmeister, “Nitric oxide regulates cardiac Ca2+ current. Involvement of cGMP- inhibited and cGMP-stimulated phosphodiesterases through guanylyl cyclase activation,” The Journal of Biological Chemistry, vol. 268, no. 35, pp. 26286–26295, 1993. View at Google Scholar · View at Scopus
  91. J. L. Balligand, R. A. Kelly, P. A. Marsden, T. W. Smith, and T. Michel, “Control of cardiac muscle cell function by an endogenous nitric oxide signaling system,” Proceedings of the National Academy of Sciences of the United States of America, vol. 90, no. 1, pp. 347–351, 1993. View at Publisher · View at Google Scholar · View at Scopus
  92. W. Shen, T. H. Hintze, and M. S. Wolin, “Nitric oxide: an important signaling mechanism between vascular endothelium and parenchymal cells in the regulation of oxygen consumption,” Circulation, vol. 92, no. 12, pp. 3505–3512, 1995. View at Google Scholar · View at Scopus
  93. Y. W. Xie, W. Shen, G. Zhao, X. Xu, M. S. Wolin, and T. H. Hintze, “Role of endothelium-derived nitric oxide in the modulation of canine myocardial mitochondrial respiration in vitro: implications for the development of heart failure,” Circulation Research, vol. 79, no. 3, pp. 381–387, 1996. View at Google Scholar · View at Scopus
  94. A. Shinbo and T. Iijima, “Potentiation by nitric oxide of the ATP-sensitive K+ current induced by K+ channel openers in guinea-pig ventricular cells,” British Journal of Pharmacology, vol. 120, no. 8, pp. 1568–1574, 1997. View at Google Scholar · View at Scopus
  95. R. Hambrecht, V. Adams, S. Erbs et al., “Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase,” Circulation, vol. 107, no. 25, pp. 3152–3158, 2003. View at Publisher · View at Google Scholar · View at Scopus
  96. D. J. Green, A. Maiorana, G. O'Driscoll, and R. Taylor, “Effect of exercise training on endothelium-derived nitric oxide function in humans,” Journal of Physiology, vol. 561, no. 1, pp. 1–25, 2004. View at Publisher · View at Google Scholar · View at Scopus
  97. C. Le Page, P. Noirez, J. Courty, B. Riou, B. Swynghedauw, and S. Besse, “Exercise training improves functional post-ischemic recovery in senescent heart,” Experimental Gerontology, vol. 44, no. 3, pp. 177–182, 2009. View at Publisher · View at Google Scholar · View at Scopus
  98. B. A. Kingwell, “Nitric oxide as a metabolic regulator during exercise: effects of training in health and disease,” Clinical and Experimental Pharmacology and Physiology, vol. 27, no. 4, pp. 239–250, 2000. View at Publisher · View at Google Scholar · View at Scopus
  99. K. E. Loke, S. K. Laycock, S. Mital et al., “Nitric oxide modulates mitochondrial respiration in failing human heart,” Circulation, vol. 100, no. 12, pp. 1291–1297, 1999. View at Google Scholar · View at Scopus
  100. Y. M. Kim, R. V. Talanian, and T. R. Billiar, “Nitric oxide inhibits apoptosis by preventing increases in caspase-3- like activity via two distinct mechanisms,” The Journal of Biological Chemistry, vol. 272, no. 49, pp. 31138–31148, 1997. View at Publisher · View at Google Scholar · View at Scopus
  101. L. Babai, Z. Szigeti, J. R. Parratt, and A. Végh, “Delayed cardioprotective effects of exercise in dogs are aminoguanidine sensitive: possible involvement of nitric oxide,” Clinical Science, vol. 102, no. 4, pp. 435–445, 2002. View at Publisher · View at Google Scholar · View at Scopus
  102. I. Momken, P. Lechêne, R. Ventura-Clapier, and V. Veksler, “Voluntary physical activity alterations in endothelial nitric oxide synthase knockout mice,” American Journal of Physiology, vol. 287, no. 2, pp. H914–H920, 2004. View at Publisher · View at Google Scholar · View at Scopus
  103. C. Ojaimi, W. Li, S. Kinugawa et al., “Transcriptional basis for exercise limitation in male eNOS-knockout mice with age: heart failure and the fetal phenotype,” American Journal of Physiology, vol. 289, no. 4, pp. H1399–H1407, 2005. View at Publisher · View at Google Scholar · View at Scopus
  104. M. C. de Waard, R. van Haperen, T. Soullié, D. Tempel, R. de Crom, and D. J. Duncker, “Beneficial effects of exercise training after myocardial infarction require full eNOS expression,” Journal of Molecular and Cellular Cardiology, vol. 48, no. 6, pp. 1041–1049, 2010. View at Publisher · View at Google Scholar · View at Scopus
  105. R. P. Taylor, M. E. Olsen, and J. W. Starnes, “Improved postischemic function following acute exercise is not mediated by nitric oxide synthase in the rat heart,” American Journal of Physiology, vol. 292, no. 1, pp. H601–H607, 2007. View at Publisher · View at Google Scholar · View at Scopus
  106. D. J. Lefer, “Nitrite therapy for protection against ischemia-reperfusion injury,” American Journal of Physiology, vol. 290, no. 4, pp. F777–F778, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. J. L. Zweier, P. Wang, A. Samouilov, and P. Kuppusamy, “Enzyme-independent formation of nitric oxide in biological tissues,” Nature Medicine, vol. 1, no. 8, pp. 804–809, 1995. View at Google Scholar · View at Scopus
  108. A. Webb, R. Bond, P. McLean, R. Uppal, N. Benjamin, and A. Ahluwalia, “Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 37, pp. 13683–13688, 2004. View at Publisher · View at Google Scholar · View at Scopus
  109. M. R. Duranski, J. J. M. Greer, A. Dejam et al., “Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver,” Journal of Clinical Investigation, vol. 115, no. 5, pp. 1232–1240, 2005. View at Publisher · View at Google Scholar · View at Scopus
  110. Y. Zhang, T. S. Lee, E. M. Kolb et al., “AMP-activated protein kinase is involved in endothelial NO synthase activation in response to shear stress,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 26, no. 6, pp. 1281–1287, 2006. View at Publisher · View at Google Scholar · View at Scopus
  111. C. Napoli, S. Williams-Ignarro, F. De Nigris et al., “Physical training and metabolic supplementation reduce spontaneous atherosclerotic plaque rupture and prolong survival in hypercholesterolemic mice,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 27, pp. 10479–10484, 2006. View at Publisher · View at Google Scholar · View at Scopus
  112. J. W. Calvert, “Cardioprotective effects of nitrite during exercise,” Cardiovascular Research, vol. 89, no. 3, pp. 499–506, 2011. View at Google Scholar
  113. J. W. Starnes and R. P. Taylor, “Exercise-induced cardioprotection: endogenous mechanisms,” Medicine and Science in Sports and Exercise, vol. 39, no. 9, pp. 1537–1543, 2007. View at Publisher · View at Google Scholar · View at Scopus
  114. J. E. Baker, S. J. Contney, R. Singh, B. Kalyanaraman, G. J. Gross, and Z. J. Bosnjak, “Nitric oxide activates the sarcolemmal Kchannel in normoxic and chronically hypoxic hearts by a cyclic GMP-dependent mechanism,” Journal of Molecular and Cellular Cardiology, vol. 33, no. 2, pp. 331–341, 2001. View at Publisher · View at Google Scholar · View at Scopus
  115. D. V. Cuong, N. Kim, J. B. Youm et al., “Nitric oxide-cGMP-protein kinase G signaling pathway induces anoxic preconditioning through activation of ATP-sensitive K+ channels in rat hearts,” American Journal of Physiology, vol. 290, no. 5, pp. H1808–H1817, 2006. View at Publisher · View at Google Scholar
  116. Q. Xu, Y. Hu, R. Kleindienst, and G. Wick, “Nitric oxide induces heat-shock protein 70 expression in vascular smooth muscle cells via activation of heat shock factor 1,” Journal of Clinical Investigation, vol. 100, no. 5, pp. 1089–1097, 1997. View at Google Scholar · View at Scopus
  117. A. Noma, “ATP-regulated K channels in cardiac muscle,” Nature, vol. 305, no. 5930, pp. 147–148, 1983. View at Google Scholar · View at Scopus
  118. Y. V. Ladilov, B. Siegmund, and H. M. Piper, “Protection of reoxygenated cardiomyocytes against hypercontracture by inhibition of Na+/H+ exchange,” American Journal of Physiology, vol. 268, no. 4, pp. H1531–H1539, 1995. View at Google Scholar · View at Scopus
  119. H. M. Piper, Y. Abdallah, and C. Schäfer, “The first minutes of reperfusion: a window of opportunity for cardioprotection,” Cardiovascular Research, vol. 61, no. 3, pp. 365–371, 2004. View at Publisher · View at Google Scholar · View at Scopus
  120. J. Inserte, D. Garcia-Dorado, V. Hernando, and J. Soler-Soler, “Calpain-mediated impairment of Na+/K+-ATPase activity during early reperfusion contributes to cell death after myocardial ischemia,” Circulation Research, vol. 97, no. 5, pp. 465–473, 2005. View at Publisher · View at Google Scholar
  121. W. J. Nelson and R. W. Hammerton, “A membrane-cytoskeletal complex containing Na+,K+-ATPase, ankyrin, and fodrin in Madin-Darby canine kidney (MDCK) cells: implications for the biogenesis of epithelial cell polarity,” Journal of Cell Biology, vol. 108, no. 3, pp. 893–902, 1989. View at Google Scholar · View at Scopus
  122. A. Skyschally, R. Schulz, and G. Heusch, “Pathophysiology of myocardial infarction. Protection by ischemic pre- and postconditioning,” Herz, vol. 33, no. 2, pp. 88–100, 2008. View at Publisher · View at Google Scholar · View at Scopus
  123. A. P. Halestrap, “Calcium, mitochondria and reperfusion injury: a pore way to die,” Biochemical Society Transactions, vol. 34, no. 2, pp. 232–237, 2006. View at Publisher · View at Google Scholar · View at Scopus
  124. W. C. Cole, C. D. McPherson, and D. Sontag, “ATP-regulated K+ channels protect the myocardium against ischemia/reperfusion damage,” Circulation Research, vol. 69, no. 3, pp. 571–581, 1991. View at Google Scholar · View at Scopus
  125. H. L. Tan, P. Mazón, H. J. Verberne et al., “Ischaemic preconditioning delays ischaemia induced cellular electrical uncoupling in rabbit myocardium by activation of ATP sensitive potassium channels,” Cardiovascular Research, vol. 27, no. 4, pp. 644–651, 1993. View at Google Scholar
  126. Z. Yao and G. J. Gross, “Activation of ATP-sensitive potassium channels lowers threshold for ischemic preconditioning in dogs,” American Journal of Physiology, vol. 267, no. 5, pp. H1888–H1894, 1994. View at Google Scholar · View at Scopus
  127. Z. Yao and G. J. Gross, “Effects of the KATP channel opener bimakalim on coronary blood flow, monophasic action potential duration, and infarct size in dogs,” Circulation, vol. 89, no. 4, pp. 1769–1775, 1994. View at Google Scholar · View at Scopus
  128. D. A. Brown, A. J. Chicco, K. N. Jew et al., “Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat,” Journal of Physiology, vol. 569, no. 3, pp. 913–924, 2005. View at Publisher · View at Google Scholar · View at Scopus
  129. A. J. Chicco, M. S. Johnson, C. J. Armstrong et al., “Sex-specific and exercise-acquired cardioprotection is abolished by sarcolemmal KATP channel blockade in the rat heart,” American Journal of Physiology, vol. 292, no. 5, pp. H2432–H2437, 2007. View at Publisher · View at Google Scholar · View at Scopus
  130. D. A. Brown, J. M. Lynch, C. J. Armstrong et al., “Susceptibility of the heart to ischaemia-reperfusion injury and exercise-induced cardioprotection are sex-dependent in the rat,” Journal of Physiology, vol. 564, no. 2, pp. 619–630, 2005. View at Publisher · View at Google Scholar · View at Scopus
  131. H. J. Ranki, G. R. Budas, R. M. Crawford, A. M. Davies, and A. Jovanović, “17β-estradiol regulates expression of KATP channels in heart-derived H9c2 cells,” Journal of the American College of Cardiology, vol. 40, no. 2, pp. 367–374, 2002. View at Publisher · View at Google Scholar · View at Scopus
  132. M. S. Johnson, R. L. Moore, and D. A. Brown, “Sex differences in myocardial infarct size are abolished by sarcolemmal KATP channel blockade in rat,” American Journal of Physiology, vol. 290, no. 6, pp. H2644–H2647, 2006. View at Publisher · View at Google Scholar · View at Scopus
  133. A. J. Chicco, M. S. Johnson, C. J. Armstrong et al., “Sex-specific and exercise-acquired cardioprotection is abolished by sarcolemmal KATP channel blockade in the rat heart,” American Journal of Physiology, vol. 292, no. 5, pp. H2432–H2437, 2007. View at Publisher · View at Google Scholar · View at Scopus
  134. S. Bae and L. Zhang, “Gender differences in cardioprotection against ischemia/reperfusion injury in adult rat hearts: focus on akt and protein kinase C signaling,” Journal of Pharmacology and Experimental Therapeutics, vol. 315, no. 3, pp. 1125–1135, 2005. View at Publisher · View at Google Scholar · View at Scopus
  135. A. G. Edwards, M. L. Rees, R. A. Gioscia et al., “PKC-permitted elevation of sarcolemmal KATP concentration may explain female-specific resistance to myocardial infarction,” Journal of Physiology, vol. 587, no. 23, pp. 5723–5737, 2009. View at Publisher · View at Google Scholar · View at Scopus
  136. K. Hu, C. S. Huang, Y. N. Jan, and L. Y. Jan, “ATP-sensitive potassium channel traffic regulation by adenosine and protein kinase C,” Neuron, vol. 38, no. 3, pp. 417–432, 2003. View at Publisher · View at Google Scholar · View at Scopus
  137. A. Jovanović, “Femininity and sarcolemmal KATP channels: a matter of the heart and the heart of the matter,” Journal of Physiology, vol. 587, no. 23, pp. 5509–5510, 2009. View at Publisher · View at Google Scholar · View at Scopus
  138. G. J. Gross and J. N. Peart, “KATP channels and myocardial preconditioning: an update,” American Journal of Physiology, vol. 285, no. 3, pp. H921–H930, 2003. View at Google Scholar · View at Scopus
  139. X. Kong, J. S. Tweddell, G. J. Gross, and J. E. Baker, “Sarcolemmal and mitochondrial KATP channels mediate cardioprotection in chronically hypoxic hearts,” Journal of Molecular and Cellular Cardiology, vol. 33, no. 5, pp. 1041–1045, 2001. View at Publisher · View at Google Scholar · View at Scopus
  140. R. M. Fryer, A. K. Hsu, and G. J. Gross, “Mitochondrial KATP channel opening is important during index ischemia and following myocardial reperfusion in ischemic preconditioned rat hearts,” Journal of Molecular and Cellular Cardiology, vol. 33, no. 4, pp. 831–834, 2001. View at Publisher · View at Google Scholar · View at Scopus
  141. K. Shinmura, K. Tamaki, T. Sato, H. Ishida, and R. Bolli, “Prostacyclin attenuates oxidative damage of myocytes by opening mitochondrial ATP-sensitive K+ channels via the EP3 receptor,” American Journal of Physiology, vol. 288, no. 5, pp. H2093–H2101, 2005. View at Publisher · View at Google Scholar · View at Scopus
  142. R. Domenech, P. Macho, H. Schwarze, and G. Sánchez, “Exercise induces early and late myocardial preconditioning in dogs,” Cardiovascular Research, vol. 55, no. 3, pp. 561–566, 2002. View at Publisher · View at Google Scholar · View at Scopus
  143. J. C. Quindry, L. Schreiber, P. Hosick, J. Wrieden, J. M. Irwin, and E. Hoyt, “Mitochondrial KATP channel inhibition blunts arrhythmia protection in ischemic exercised hearts,” American Journal of Physiology, vol. 299, no. 1, pp. H175–H183, 2010. View at Publisher · View at Google Scholar · View at Scopus
  144. S. Judge, Y. M. Jang, A. Smith et al., “Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart,” American Journal of Physiology, vol. 289, no. 6, pp. R1564–R1572, 2005. View at Publisher · View at Google Scholar · View at Scopus
  145. J. W. Starnes, B. D. Barnes, and M. E. Olsen, “Exercise training decreases rat heart mitochondria free radical generation but does not prevent Ca2+-induced dysfunction,” Journal of Applied Physiology, vol. 102, no. 5, pp. 1793–1798, 2007. View at Publisher · View at Google Scholar · View at Scopus
  146. M. Marcil, K. Bourduas, A. Ascah, and Y. Burelle, “Exercise training induces respiratory substrate-specific decrease in Ca2+-induced permeability transition pore opening in heart mitochondria,” American Journal of Physiology, vol. 290, no. 4, pp. H1549–H1557, 2006. View at Publisher · View at Google Scholar
  147. A. N. Kavazis, J. M. McClung, D. A. Hood, and S. K. Powers, “Exercise induces a cardiac mitochondrial phenotype that resists apoptotic stimuli,” American Journal of Physiology, vol. 294, no. 2, pp. H928–H935, 2008. View at Publisher · View at Google Scholar · View at Scopus
  148. S. Ghosh, M. Khazaei, F. Moien-Afshari et al., “Moderate exercise attenuates caspase-3 activity, oxidative stress, and inhibits progression of diabetic renal disease in db/db mice,” American Journal of Physiology, vol. 296, no. 4, pp. F700–F708, 2009. View at Publisher · View at Google Scholar · View at Scopus
  149. M. B. H. Youdim and J. P. M. Finberg, “New directions in monoamine oxidase A and B: selective inhibitors and substrates,” Biochemical Pharmacology, vol. 41, no. 2, pp. 155–162, 1991. View at Publisher · View at Google Scholar · View at Scopus
  150. A. Maurel, C. Hernandez, O. Kunduzova et al., “Age-dependent increase in hydrogen peroxide production by cardiac monoamine oxidase A in rats,” American Journal of Physiology, vol. 284, no. 4, pp. H1460–H1467, 2003. View at Google Scholar · View at Scopus
  151. S. W. Kong, N. Bodyak, P. Yue et al., “Genetic expression profiles during physiological and pathological cardiac hypertrophy and heart failure in rats,” Physiological Genomics, vol. 21, pp. 34–42, 2005. View at Publisher · View at Google Scholar · View at Scopus
  152. P. Bianchi, O. Kunduzova, E. Masini et al., “Oxidative stress by monoamine oxidase mediates receptor-independent cardiomyocyte apoptosis by serotonin and postischemic myocardial injury,” Circulation, vol. 112, no. 21, pp. 3297–3305, 2005. View at Publisher · View at Google Scholar · View at Scopus
  153. D. Pchejetski, O. Kunduzova, A. Dayon et al., “Oxidative stress-dependent sphingosine kinase-1 inhibition mediates monoamine oxidase A-associated cardiac cell apoptosis,” Circulation Research, vol. 100, no. 1, pp. 41–49, 2007. View at Publisher · View at Google Scholar · View at Scopus
  154. A. N. Kavazis, S. Alvarez, E. Talbert, Y. Lee, and S. K. Powers, “Exercise training induces a cardioprotective phenotype and alterations in cardiac subsarcolemmal and intermyofibrillar mitochondrial proteins,” American Journal of Physiology, vol. 297, no. 1, pp. H144–H152, 2009. View at Publisher · View at Google Scholar · View at Scopus
  155. N. R. Brady, A. Hamacher-Brady, H. Yuan, and R. A. Gottlieb, “The autophagic response to nutrient deprivation in the hl-1 cardiac myocyte is modulated by Bcl-2 and sarco/endoplasmic reticulum calcium stores,” FEBS Journal, vol. 274, no. 12, pp. 3184–3197, 2007. View at Publisher · View at Google Scholar · View at Scopus
  156. M. Tsukada and Y. Ohsumi, “Isolation and characterization of autophagy-defective mutants of Saccharomyces cerevisiae,” FEBS Letters, vol. 333, no. 1-2, pp. 169–174, 1993. View at Publisher · View at Google Scholar · View at Scopus
  157. Z. Yue, S. Jin, C. Yang, A. J. Levine, and N. Heintz, “Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 25, pp. 15077–15082, 2003. View at Publisher · View at Google Scholar · View at Scopus
  158. R. A. Nixon, J. Wegiel, A. Kumar et al., “Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study,” Journal of Neuropathology and Experimental Neurology, vol. 64, no. 2, pp. 113–122, 2005. View at Google Scholar · View at Scopus
  159. J. L. Webb, B. Ravikumar, J. Atkins, J. N. Skepper, and D. C. Rubinsztein, “α-Synuclein is degraded by both autophagy and the proteasome,” The Journal of Biological Chemistry, vol. 278, no. 27, pp. 25009–25013, 2003. View at Publisher · View at Google Scholar · View at Scopus
  160. L. Yan, D. E. Vatner, S. J. Kim et al., “Autophagy in chronically ischemic myocardium,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 39, pp. 13807–13812, 2005. View at Publisher · View at Google Scholar · View at Scopus
  161. P. Saftig, K. Von Figura, Y. Tanaka, and R. Lüllmann-Rauch, “Disease model: LAMP-2 enlightens Danon disease,” Trends in Molecular Medicine, vol. 7, no. 1, pp. 37–39, 2000. View at Publisher · View at Google Scholar · View at Scopus
  162. L. Xue, G. C. Fletcher, and A. M. Tolkovsky, “Mitochondria are selectively eliminated from eukaryotic cells after blockade of caspases during apoptosis,” Current Biology, vol. 11, no. 5, pp. 361–365, 2001. View at Publisher · View at Google Scholar · View at Scopus
  163. S. Shimizu, T. Kanaseki, N. Mizushima et al., “Role of Bcl-2 family proteins in a non-apoptopic programmed cell death dependent on autophagy genes,” Nature Cell Biology, vol. 6, no. 12, pp. 1221–1228, 2004. View at Publisher · View at Google Scholar · View at Scopus
  164. W. Dröge and H. M. Schipper, “Oxidative stress and aberrant signaling in aging and cognitive decline,” Aging Cell, vol. 6, no. 3, pp. 361–370, 2007. View at Publisher · View at Google Scholar · View at Scopus
  165. G. J. Etgen, B. A. Oldham, W. T. Johnson et al., “A tailored therapy for the metabolic syndrome: the dual peroxisome proliferator-activated receptor-α/γ agonist LY465608 ameliorates insulin resistance and diabetic hyperglycemia while improving cardiovascular risk factors in preclinical models,” Diabetes, vol. 51, no. 4, pp. 1083–1087, 2002. View at Google Scholar
  166. G. L. Dohm, E. B. Tapscott, and G. J. Kasperek, “Protein degradation during endurance exercise and recovery,” Medicine and Science in Sports and Exercise, vol. 19, no. 5, pp. S166–171, 1987. View at Google Scholar · View at Scopus
  167. J. P. French, K. L. Hamilton, J. C. Quindry, Y. Lee, P. A. Upchurch, and S. K. Powers, “Exercise-induced protection against myocardial apoptosis and necrosis: MnSOD, calcium-handling proteins, and calpain,” FASEB Journal, vol. 22, no. 8, pp. 2862–2871, 2008. View at Publisher · View at Google Scholar · View at Scopus
  168. A. Kawai, H. Uchiyama, S. Takano, N. Nakamura, and S. Ohkuma, “Autophagosome-lysosome fusion depends on the pH in acidic compartments in CHO cells,” Autophagy, vol. 3, no. 2, pp. 154–157, 2007. View at Google Scholar · View at Scopus
  169. M. G. MacKenzie, D. L. Hamilton, J. T. Murray, and K. Baar, “mVps34 is activated by an acute bout of resistance exercise,” Biochemical Society Transactions, vol. 35, no. 5, pp. 1314–1316, 2007. View at Publisher · View at Google Scholar · View at Scopus
  170. D. K. Arrell, S. T. Elliott, L. A. Kane et al., “Proteomic analysis of pharmacological preconditioning: novel protein targets converge to mitochondrial metabolism pathways,” Circulation Research, vol. 99, no. 7, pp. 706–714, 2006. View at Publisher · View at Google Scholar · View at Scopus
  171. M. G. Mackenzie, D. L. Hamilton, J. T. Murray, P. M. Taylor, and K. Baar, “mVps34 is activated following high-resistance contractions,” Journal of Physiology, vol. 587, no. 1, pp. 253–260, 2009. View at Publisher · View at Google Scholar · View at Scopus
  172. N. Gurusamy, I. Lekli, N. V. Gorbunov, M. Gherghiceanu, L. M. Popescu, and D. K. Das, “Cardioprotection by adaptation to ischaemia augments autophagy in association with BAG-1 protein,” Journal of Cellular and Molecular Medicine, vol. 13, no. 2, pp. 373–387, 2009. View at Publisher · View at Google Scholar · View at Scopus
  173. B. O'Rourke, S. Cortassa, and M. A. Aon, “Mitochondrial ion channels: gatekeepers of life and death,” Physiology, vol. 20, no. 5, pp. 303–315, 2005. View at Google Scholar · View at Scopus
  174. H. M. Honda, P. Korge, and J. N. Weiss, “Mitochondria and ischemia/reperfusion injury,” Annals of the New York Academy of Sciences, vol. 1047, pp. 248–258, 2005. View at Publisher · View at Google Scholar · View at Scopus