Current Problems in Cardiology
Volume 31, Issue 3 , Pages 181-264 , March 2006

Clinical Implications of Apoptosis in Ischemic Myocardium

References 

  1. Van Cruchten S , Van der Broeck W . Morphological and biochemical aspects of apoptosis, oncosis and necrosis . Anat Histol Embryol . 2002;31:214–223
  2. Farber E . Ideas in pathology: programmed cell death: necrosis versus apoptosis . Mod Pathol . 1994;7:605–609
  3. Clarke PG , Clarke S . Nineteenth century research on naturally occurring cell death and related phenomena . Anat Embryol . 1996;193:81–99
  4. Kerr JFR . Shrinking necrosis (a distinct mode of cell death) . J Pathol . 1971;105:13–20
  5. Stergiou L , Hengartner MO . Death and more (DNA damage response pathways in the nematode C. elegans) . Cell Death Differ . 2004;11:21–28
  6. Gustafsson AB , Gottlieb RA . Mechanisms of apoptosis in the heart . J Clin Immunol . 2003;23:447–459
  7. Fulda S , Debatin K-M . Signaling through death receptors in cancer therapy . Curr Opin Pharmacol . 2004;4:327–332
  8. Thorburn A . Death receptor-induced cell killing . Cell Signal . 2004;16:139–144
  9. Meldrum DR . Tumor necrosis factor in the heart . Am J Physiol . 1998;274:R577–R595
  10. Spierings DC , de Vries EG , Vellenga E , et al.   Tissue distribution of the death ligand TRAIL and its receptors . J Histochem Cytochem . 2004;52:821–831
  11. Hengartner MO . The biochemistry of apoptosis . Nature . 2000;407:770–776
  12. Krammer PH . CD95s deadly mission to the immune system . Nature . 2000;407:789–795
  13. Barnhart BC , Lee JC , Alappat EC , et al.   The death effector domain protein family . Oncogene . 2003;22:8634–8644
  14. Irmler M , Thome M , Hahne M , et al.   Inhibition of death receptor signals by cellular FLIP . Nature . 1997;386:517–521
  15. Krueger P , Schmitz I , Baumann S , et al.   Cellular FLICE-like inhibitory protein splice variants inhibit different steps of caspase-8 activation at the CD95 death-inducing signalling complex . J Biol Chem . 2001;276:20633–20640
  16. Imanashi T , Murry CE , Reinecke H , et al.   Cellular FLIP is expressed in cardiac myocytes and down-regulated in TUNEL-positive grafted cardiac tissues . Cardiovasc Res . 2000;48:101–110
  17. Sheikh MS , Huang Y . Death receptor activation complexes (it takes two to activate receptor 1) . Cell Cycle . 2003;2:550–552
  18. Wajant H . TRAIL and NFkappaB signalling . Vitam Horm . 2004;67:101–132
  19. Natoli G , Costanzo A , Moretti F , et al.   Tumor Necrosis Factor (TNF) receptor 1 signalling downstream of TNF receptor-associated factor 2. Nuclear factor kappaB but not c-Jun N-terminal kinase/stress-activated protein kinase . J Biol Chem . 1997;272:26079–26082
  20. Beg AA , Baltimore D . An essential role for NF-kappaB in preventive TNF-alpha-induced cell death . Science . 1996;274:782–784
  21. Antwerp DJV , Martin SJ , Kafri T , et al.   Suppression of TNF-alpha-induced apoptosis by NF-kappaB . Science . 1996;274:787–789
  22. Saelens X , Festjens N , Vande Walle L , et al.   Toxic proteins released from mitochondria in cell death . Oncogene . 2004;23:2861–2874
  23. Esposti MD . The roles of Bid . Apoptosis . 2002;7:433–440
  24. Jiang X , Wang X . Cytochrome c-mediated apoptosis . Annu Rev Biochem . 2004;73:87–106
  25. Adrain C , Martin CJ . The mitochondrial apoptosome (a killer unleashed by the cytochrome) . Trends Biochem Sci . 2001;26:390–397
  26. Adams JM , Cory S . Apoptosomes (engines for caspase activation) . Curr Opin Cell Biol . 2002;14:715–720
  27. Green DR , Kroemer G . The central executioners of apoptosis (caspases or mitochondria?) . Cell Biol . 1998;8:267–271
  28. Cory S , Adams JM . The Bcl2 family (regulators of the cellular life-or-death switch) . Nat Rev Cancer . 2002;2:647–656
  29. Huang DCS , Strasser A . BH3-only proteins—essential initiators of apoptotic cell death . Cell . 2000;103:839–842
  30. Liston P , Fong WG , Korneluk RG . The inhibitors of apoptosis (there is more to life than Bcl2) . Oncogene . 2003;22:8568–8580
  31. Nagata S , Nagase H , Kawane K , et al.   Degradation of chromosomal DNA during apoptosis . Cell Death Differ . 2003;10:108–116
  32. Riedl SJ , Shi Y . Molecular mechanisms of caspase regulation during apoptosis . Nat Rev Mol Cell Biol . 2004;5:897–907
  33. Fischer U , Janicke RU , Schulze-Osthoff K . Many cuts to ruin (a comprehensive update of caspase substrates) . Cell Death Differ . 2003;10:76–100
  34. Gozuacik D , Kimchi A . Autophagy as a cell death and tumour suppressor mechanism . Oncogene . 2004;23:2891–2906
  35. Kuma A , Hatano M , Matsui M , et al.   The role of autophagy during the early neonatal starvation period . Nature . 2004;432:1032–1036
  36. Decker RS , Wildenthal K . Lysosomal alterations in hypoxic and reoxygenated hearts. I . Ultrastructural and cytochemical changes Am J Pathol . 1980;98:425–444
  37. Liu X , Van Vleet T , Schnellmann RG . The role of calpain in oncotic cell death . Annu Rev Pharmacol Toxicol . 2004;44:349–370
  38. Levrero M , De Laurenzi V , Costanzo A , et al.   The p53/p63/p73 family of transcription factors (overlapping and distinct functions) . J Cell Sci . 2000;113:1661–1670
  39. Darnell JE . STATs and gene regulation . Science . 1997;277:1630–1635
  40. Ihle JN . The Stat family in cytokine signaling . Curr Opin Cell Biol . 2001;13:211–217
  41. Yasukawa H , Sasaki A , Yoshimura A . Negative regulation of cytokine signaling pathways . Annu Rev Immunol . 2000;18:143–164
  42. Krebs DL , Hilton DJ . SOCS (physiological suppressors of cytokine signaling) . J Cell Sci . 2000;113:2813–2819
  43. Greenhalgh CJ , Hilton DJ . Negative regulation of cytokine signaling . J Leukoc Biol . 2001;70:348–356
  44. Liu B , Liao J , Rao X , et al.   Inhibition of Stat1-mediated gene activation by PIAS1 . Proc Natl Acad Sci USA . 1998;95:10626–10631
  45. Chung CD , Liao J , Liu B , et al.   Specific inhibition of Stat3 signal transduction by PIAS3 . Science . 1997;278:1803–1805
  46. Kunisada K , Hirota H , Fujio Y , et al.   Activation of the JAK-STAT and MAP kinase by leukemia inhibitory factor through gp130 in cardiac myocytes . Circulation . 1996;94:2626–2632
  47. Pan J , Fukada K , Kodama H , et al.   Role of angiotensin II in activation of the JAK/STAT pathway induced by acute pressure overload in the rat heart . Circ Res . 1997;81:199–208
  48. Xuan YT , Guo Y , Han H , et al.   An essential role of the JAK-STAT pathway in ischaemic preconditioning . Proc Natl Acad Sci USA . 2001;98:9050–9055
  49. Smith RM , Suleman N , Lacerda L , et al.   Genetic depletion of cardiac myocyte STAT-3 abolishes classical preconditioning . Cardiovasc Res . 2004;63:611–616
  50. Stephanou A , Brar BK , Scarabelli T , et al.   Ischemia-induced STAT-1 expression and activation plays a critical role in cardiac myocyte apoptosis . J Biol Chem . 2000;275:10002–10008
  51. Stephanou A , Scarabelli T , Brar BK , et al.   Induction of apoptosis and Fas/FasL expression by ischaemia/reperfusion in cardiac myocytes requires serine 727 of the STAT1 but not tyrosine 701 . J Biol Chem . 2001;276:28340–28347
  52. Negro S , Kunisada K , Tone E , et al.   Activation of the JAK/STAT pathway transduces cytoprotective signal in rat acute myocardial infarction . Cardiovasc Res . 2000;47:797–805
  53. Stephanou A , Brar B , Heads R , et al.   Cardiotropin-1 induces heat shock accumulation in cultured cardiac cells and protects them from stressful stimuli . J Mol Cell Cardiol . 1998;30:849–855
  54. Liao Z , Brar BK , Cai Q , et al.   Cardiotrophin-1 (CT-1) can protect the adult heart from injury when added both prior to ischaemia and at reperfusion . Cardiovasc Res . 2002;53:902–910
  55. Hilfiker-Kleiner D , Hilfiker A , Fuchs M , et al.   Signal transducer and activator of transcription 3 is required for myocardial capillary growth, control of interstitial matrix deposition, and heart protection from ischemic injury . Circ Res . 2004;95:187–195
  56. Jacoby JJ , Kalinowski A , Liu MG , et al.   Cardiomyocyte-restricted knockout of STAT3 results in higher sensitivity to inflammation, cardiac fibrosis, and heart failure with advanced age . Proc Natl Acad Sci USA . 2003;100:12929–12934
  57. Stephanou A , Brar BK , Knight RA , et al.   Opposing actions of STAT-1 and STAT-3 on the Bcl-2 and Bcl-x promoters . Cell Death Differ . 2000;7:329–330
  58. DaFonseca CJ , Shu F , Zhang JJ . Identification of two residues in MCM5 critical for the assembly of MCM complexes and Stat1-mediated transcription activation in response to IFN-gamma . Proc Natl Acad Sci USA . 2001;98:3034–3039
  59. Ouchi T , Lee SW , Ouchi M , et al.   Collaboration of signal transducer and activator of transcription 1 (STAT1) and BRCA1 in differential regulation of IFN-gamma target genes . Proc Natl Acad. Sci USA . 2000;97:5208–5213
  60. Townsend PA , Scarabelli TM , Davidson SM , et al.   STAT-1 interacts with p53 to enhance DNA damage-induced apoptosis . J Biol Chem . 2004;279:5811–5820
  61. Lin J , Tang H , Jin X , et al.   p53 regulates Stat3 phosphorylation and DNA binding activity in human prostate cancer cells expressing constitutively active Stat3 . Oncogene . 2002;21:3082–3088
  62. Stephanou A, Scarabelli T, Townsend PA, et al. The carboxyl-terminal activation domain of the STAT-1 transcription factor enhances ischaemia/reperfusion-induced apoptosis in cardiac myocytes. FASEB J 16:1841-3.
  63. King P , Goodbourn S . STAT1 is inactivated by a caspase . J Biol Chem . 1998;273:8699–8704
  64. Menegazzi M , Tedeschi E , Dussin D , et al.   Anti-interferon gamma action of epigallocatechin-3-gallate mediated by specific inhibition of STAT1 activation . FASEB J . 2001;15:1309–1311
  65. Townsend PA , Scarabelli TM , Pasini E , et al.   Epigallocatechin-3-gallate inhibits STAT-1 activation and protects cardiac myocytes from ischemia/reperfusion-induced apoptosis . FASEB J . 2004;18:1621–1623
  66. Takayama S , Sato T , Krajewski S , et al.   Cloning and functional analysis of Bag-1 (a novel Bcl-2-binding protein with anti-cell death activity) . Cell . 1995;80:279–284
  67. Zeiner M , Gehring U . A protein that interacts with members of the nuclear hormone receptor family (identification and cDNA cloning) . Proc Natl Acad Sci USA . 1995;92:11465–11469
  68. Townsend PA , Cutress RI , Sharp A , et al.   Bag-1 (a multifunctional regulator of cell growth and survival) . Biochim Biophys Acta . 2003;1603:83–98
  69. Townsend PA , Cutress RI , Brimmell M , et al.   Bag-1 prevents stress-induced long term growth inhibition in breast cancer cells via a chaperone-dependent pathway . Cancer Res . 2003;63:4150–4157
  70. Townsend PA , Dublin E , Hart IR , et al.   Bag-1 expression in human breast cancer (Inter-relationship between Bag-1 RNA, protein, Hsc-70 expression and clinico-pathological data) . J Pathol . 2002;197:51–59
  71. Cutress RI , Townsend PA , Brimmell M , et al.   Bag-1 expression and function in human cancer . Br J Cancer . 2002;87:834–839
  72. Townsend PA , Stephanou A , Packham G , et al.   Bag-1 (a multi-functional pro-survival molecule) . Int J Biochem Cell Biol . 2005;37:251–259
  73. Packham G , Brimmell M , Cleveland JL . Mammalian cells express two differently localized Bag-1 isoforms generated by alternative translation initiation . Biochem J . 1997;328:807–813
  74. Takayama S , Reed J . Molecular chaperone targeting and regulation by Bag family proteins . Nat Cell Biol . 2001;3:237–241
  75. Sondermann H , Scheufler C , Schneider C , et al.   Structure of a Bag-1/Hsc70 complex (convergent functional evolution of HSP70 nucleotide exchange factors) . Science . 2001;291:1553–1557
  76. Briknarova K , Takayama S , Brive L , et al.   Structural analysis of Bag-1 cochaperone and its interactions with HSC70 heat shock protein . Nat Struct Biol . 2001;8:349–352
  77. Demand J , Alberti S , Patterson C , et al.   Cooperation of a ubiquitin domain protein and an E3 ubiquitin ligase during chaperone/proteasome coupling . Curr Biol . 2001;11:1569–1577
  78. Alberti S , Demand J , Esser C , et al.   Ubiquitylation of Bag-1 suggests a novel regulatory mechanism during the sorting of chaperone substrates to the proteasome . J Biol Chem . 2002;277:45920–45927
  79. Niyaz Y , Frenz I , Petersen G , et al.   Transcriptional stimulation by the DNA binding protein Hap46/Bag-1M involves Hsp70/Hsc70 molecular chaperones . Nucleic Acids Res . 2003;31:2209–2216
  80. Crocoll A , Blum M , Cato AC . Isoform-specific expression of Bag-1 in mouse development . Mech Dev . 2000;91:355–359
  81. Townsend PA , Cutress RI , Carroll CJ , et al.   Bag-1 proteins protect cardiac myocytes from simulated ischemia/reperfusion-induced apoptosis via an alternate mechanism of cell survival independent of the proteasome . J Biol Chem . 2004;279:20723–20728
  82. Ohno M , Takemura G , Ohno A , et al.   “Apoptotic” myocytes in infarct area in rabbit hearts may be oncotic myocytes with DNA fragmentation (analysis by immunogold electron microscopy combined with in situ nick end-labeling) . Circulation . 1998;98:1422–1430
  83. Neuss M , Crow MT , Chesley A , et al.   Apoptosis in cardiac disease—what is it—how does it occur . Cardiovasc Drugs Ther . 2001;15:507–523
  84. Gottlieb RA , Burleson KO , Kloner RA , et al.   Reperfusion injury induces apoptosis in rabbit cardiomyocytes . J Clin Invest . 1994;94:1621–1628
  85. Kajstura J , Cheng W , Reiss K , et al.   Apoptotic and necrotic myocyte cell death are independent contributing variables of infarct size in rats . Lab Invest . 1996;74:86–107
  86. Zhao ZQ , Vinten-Johansen J . Myocardial apoptosis and ischemic preconditioning . Cardiovasc Res . 2002;55:438–455
  87. Scarabelli T , Stephanou A , Rayment N , et al.   Apoptosis of endothelial cells precedes myocyte cell apoptosis in ischaemia/reperfusion injury . Circulation . 2001;104:253–256
  88. Bussani R , Abbate A , Biondi-Zoccai GG , et al.   Right ventricular dilatation after left ventricular acute myocardial infarction is predictive of extremely high peri-infarctual apoptosis at postmortem examination in humans . J Clin Pathol . 2003;56:672–676
  89. Scarabelli TM , Pasini E , Ferrari G , et al.   Warm blood cardioplegic arrest induces mitochondrial-mediated cardiomyocyte apoptosis associated with increased urocortin expression in viable cells . J Thorac Cardiovasc Surg . 2004;128:364–371
  90. Zhao ZQ , Morris CD , Budde JM , et al.   Inhibition of myocardial apoptosis reduces infarct size and improves regional contractile dysfunction during reperfusion . Cardiovasc Res . 2003;59:132–142
  91. Dumont EA , Hofstra L , van Heerde WL , et al.   Cardiomyocyte death induced by myocardial ischemia and reperfusion (measurement with recombinant human annexin-V in a mouse model) . Circulation . 2000;102:1564–1568
  92. Dumont EA , Reutelingsperger CP , Smits JF , et al.   Real-time imaging of apoptotic cell-membrane changes at the single-cell level in the beating murine heart . Nat Med . 2001;7:1352–1355
  93. Hofstra L , Liem IH , Dumont EA , et al.   Visualisation of cell death in vivo in patients with acute myocardial infarction . Lancet . 2000;356:209–212
  94. Eefting F , Rensing B , Wigman J , et al.   Role of apoptosis in reperfusion injury . Cardiovasc Res . 2004;61:414–426
  95. Holly TA , Drincic A , Byun Y , et al.   Caspase inhibition reduces myocyte cell death induced by myocardial ischemia and reperfusion in vivo . J Mol Cell Cardiol . 1999;31:1709–1715
  96. Cesselli D , Jakoniuk I , Barlucchi L , et al.   Oxidative stress-mediated cardiac cell death is a major determinant of ventricular dysfunction and failure in dog dilated cardiomyopathy . Circ Res . 2001;89:279–286
  97. Gustafsson AB , Gottlieb RA . Mechanisms of apoptosis in the heart . J Clin Immunol . 2003;23:447–459
  98. Yaoita H , Ogawa K , Maehara K , et al.   Attenuation of ischaemia/reperfusion injury in rats by a caspase inhibitor . Circulation . 1998;97:276–281
  99. Mocanu MM , Baxter GF , Yellon DM . Caspase inhibition and limitation of myocardial infarct size (protection against lethal reperfusion injury) . Br J Pharmacol . 2000;130:197–200
  100. Chandrashekhar Y , Sen S , Anway R , et al.   Long-term caspase inhibition ameliorates apoptosis, reduces myocardial troponin-I cleavage, protects left ventricular function, and attenuates remodeling in rats with myocardial infarction . J Am Coll Cardiol . 2004;43:295–301
  101. Condorelli G , Roncarati R , Ross J , et al.   Heart-targeted overexpression of caspase3 in mice increases infarct size and depresses cardiac function . Proc Natl Acad Sci USA . 2001;98:9977–9982
  102. Baldi A , Abbate A , Bussani R , et al.   Apoptosis and post-infarction left ventricular remodeling . J Mol Cell Cardiol . 2002;34:165–174
  103. Elsasser A , Greiber S , Hein S , et al.   Hibernating myocardium (upregulation of the caspase-3 gene and reduction of bcl-2) . Circulation . 1999;100(suppl I):3999
  104. Stephanou AS , Brar BK , Scarabelli T , et al.   Distinct initiator caspases are required for the induction of apoptosis in cardiac myocytes in ischaemia versus reperfusion injury . Cell Death Differ . 2001;8:434–435
  105. Scarabelli TM , Stephanou A , Pasini E , et al.   Different signalling pathways induce apoptosis in endothelial cells and cardiac myocytes during ischaemia/reperfusion injury . Circ Res . 2002;90:745–748
  106. Scarabelli TM , Stephanou A , Pasini E , et al.   Minocycline inhibits caspase activation and reactivation, increases the ratio of XIAP to smac/DIABLO, and reduces the mitochondrial leakage of cytochrome C and smac/DIABLO . J Am Coll Cardiol . 2004;43:865–874
  107. Narula J , Pandey P , Arbustini E , et al.   Apoptosis in heart failure (Release of cytochrome c from mitochondria and activation of caspase-3 in human cardiomyopathy) . Proc Natl Acad Sci USA . 1999;96:8144–8149
  108. Scheubel RJ , Bartling B , Simm A , et al.   Apoptotic pathway activation from mitochondria and death receptors without caspase-3 cleavage in failing human myocardium (fragile balance of myocyte survival?) . J Am Coll Cardiol . 2002;39:481–488
  109. Borutaite V , Jekabsone A , Morkuniene R , et al.   Inhibition of mitochondrial permeability transition prevents mitochondrial dysfunction, cytochrome c release and apoptosis induced by heart ischemia . J Mol Cell Cardiol . 2003;35:357–366
  110. Borutaite V , Budriunaite A , Morkuniene R , et al.   Release of mitochondrial cytochrome c and activation of cytosolic caspases induced by myocardial ischaemia . Biochim Biophys Acta . 2001;1537:101–109
  111. Jeremias I , Kupatt C , Martin-Villaba A , et al.   Involvement of CD95/Apo1/Fas in cell death after myocardial ischaemia . Circulation . 2000;102:915–920
  112. Yamaguchi S , Yamaoka M , Okuyama M , et al.   Elevated circulating levels and cardiac secretion of soluble Fas ligand in patients with congestive heart failure . Am J Cardiol . 1999;15:1500–1503
  113. Nishigaki K , Minatoguchi S , Seishima M , et al.   Plasma Fas ligand, an inducer of apoptosis, and plasma soluble Fas, an inhibitor of apoptosis, in patients with chronic congestive heart failure . J Am Coll Cardiol . 1997;29:1214–1220
  114. Schumann H , Morawietz H , Hakim K , et al.   Alternative splicing of the primary Fas transcript generating soluble Fas antagonists is suppressed in the failing human ventricular myocardium . Biochem Biophys Res Commun . 1997;239:794–798
  115. Lee P , Sata M , Lefer DJ , et al.   Fas pathway is a critical mediator of cardiac myocyte death and MI during ischemia-reperfusion in vivo . Am J Physiol Heart Circ Physiol . 2003;284:H456–H463
  116. Chen Z , Chua CC , Ho YS , et al.   Overexpression of Bcl-2 attenuates apoptosis and protects against myocardial I/R injury in transgenic mice . Am J Physiol Heart Circ Physiol . 2001;280:H2313–H2320
  117. Chatterjee S , Stewart AS , Bish LT , et al.   Viral gene transfer of the antiapoptotic factor Bcl-2 protects against chronic postischemic heart failure . Circulation . 2002;106:I212–I217
  118. Kang PM , Haunstetter A , Aoki H , et al.   Morphological and molecular characterization of adult cardiomyocyte apoptosis during hypoxia and reoxygenation . Circ Res . 2000;87:118–125
  119. Pain T , Yang XM , Critz SD , et al.   Opening of mitochondrial KATP channels triggers the preconditioned state by generating free radicals . Circ Res . 2000;87:460–466
  120. Wang NP , Bufkin BL , Nakamura M , et al.   Ischemic preconditioning reduces neutrophil accumulation and myocardial apoptosis . Ann Thoracic Surg . 1999;67:1689–1695
  121. Akao M , Ohler A , O’Rourke B , et al.   Mitochondrial ATP-sensitive potassium channels inhibit apoptosis induced by oxidative stress in cardiac cells . Circ Res . 2001;88:1267–1275
  122. Mathur P , Kaga S , Zhan L , et al.   Antibody-array technique reveals overexpression of important DNA-repair proteins during cardiac ischemic preconditioning . J Mol Cell Cardiol . 2005;38:99–102
  123. Sergeev P , Da Silva R , Lucchinetti E , et al.   Trigger-dependent gene expression profiles in cardiac preconditioning (evidence for distinct genetic programs in ischemic and anesthetic preconditioning) . Anesthesiology . 2004;100:474–488
  124. Simkhovich BZ , Marjoram P , Poizat C , et al.   Brief episode of ischemia activates protective genetic program in rat heart (a gene chip study) . Cardiovasc Res . 2003;59:450–459
  125. Onody A , Zvara A , Hackler L , et al.   Effect of classic preconditioning on the gene expression pattern of rat hearts (a DNA microarray study) . FEBS Lett . 2003;536:35–40
  126. Simkhovich BZ , Abdishoo S , Poizat C , et al.   Gene activity changes in ischemically preconditioned rabbit heart gene (discovery array study) . Heart Dis . 2002;4:63–69
  127. Steenbergen C , Perlman ME , London RE , et al.   Mechanism of preconditioning (ionic alterations) . Circ Res . 1993;72:112–125
  128. Murphy E , Perlman M , London RE , et al.   Amiloride delays the ischemia-induced rise in cytosolic free calcium . Circ Res . 1991;68:1250–1258
  129. Karmazyn M . The role of the myocardial sodium-hydrogen exchanger in mediating ischemic and reperfusion injury. From amiloride to cariporide . Ann NY Acad Sci . 1999;874:326–334
  130. Buttgereit F , Brand MD . A hierarchy of ATP-consuming processes in mammalian cells . Biochem J . 1995;312:163–167
  131. Wieser W , Krumschnabel G . Hierarchies of ATP-consuming processes (direct compared with indirect measurements, and comparative aspects) . Biochem J . 2001;355:389–395
  132. An J , Varadarajan SG , Novalija E , et al.   Ischemic and anesthetic preconditioning reduces cytosolic [Ca2+] and improves Ca2+ responses in intact hearts . Am J Physiol Heart Circ Physiol . 2001;281:H1508–H1523
  133. Pilane CM , LaBelle EF . cPLA2 activator peptide, PLAP, increases arachidonic acid release and apoptosis of vascular smooth muscle cells . J Cell Physiol . 2004;198:48–52
  134. Penzo D , Petronilli V , Angelin A , et al.   Arachidonic acid released by phospholipase A2 activation triggers Ca2+-dependent apoptosis through the mitochondrial pathway . J Biol Chem . 2004;279:25219–25225
  135. Gross ER , Nithipatikom K , Hsu AK , et al.   Cytochrome P450 omega-hydroxylase inhibition reduces infarct size during reperfusion via the sarcolemmal K(ATP) channel . J Mol Cell Cardiol . 2004;37:1245–1249
  136. Alexander LD , Cui XL , Falck JR , et al.   Arachidonic acid directly activates members of the mitogen-activated protein kinase superfamily in rabbit proximal tubule cells . Kidney Int . 2001;59:2039–2053
  137. Roman RJ . P-450 metabolites of arachidonic acid in the control of cardiovascular function . Physiol Rev . 2002;82:131–185
  138. Chen M , He H , Zhan S , et al.   Bid is cleaved by calpain to an active fragment in vitro and during myocardial ischemia/reperfusion . J Biol Chem . 2001;276:30724–30728
  139. Tsuji T , Ohga Y , Yoshikawa Y , et al.   Rat cardiac contractile dysfunction induced by Ca2+ overload (possible link to the proteolysis of α-fodrin) . Am J Physiol Heart Circ Physiol . 2001;281:H1286–H1294
  140. Murphy AN , Bredesen DE , Cortopassi G , et al.   Bcl-2 potentiates the maximal calcium uptake capacity of neural cell mitochondria . Proc Natl Acad Sci USA . 1996;93:9893–9898
  141. Wang HG , Pathan N , Ethell IM , et al.   Ca2+-induced apoptosis through calcineurin dephosphorylation of BAD . Science . 1999;284:339–343
  142. Chen M , Won DJ , Krajewski S , et al.   Calpain and mitochondria in ischemia/reperfusion injury . J Biol Chem . 2002;277:29181–29186
  143. Kobayashi S , Yoshikawa Y , Sakata S , et al.   Left ventricular mechanoenergetics after hyperpolarized cardioplegic arrest by nicorandil and after depolarized cardioplegic arrest by KCl . Am J Physiol Heart Circ Physiol . 2004;287:H1072–H1080
  144. Asimakis GK , Inners-McBride K , Medellin G , et al.   Ischemic preconditioning attenuates acidosis and postischemic dysfunction in isolated rat heart . Am J Physiol . 1992;263:H887–H894
  145. Finegan BA , Lopaschuk GD , Gandhi M , et al.   Ischemic preconditioning inhibits glycolysis and proton production in isolated working rat hearts . Am J Physiol . 1995;269:H1767–H1775
  146. Kubasiak LA , Hernandez OM , Bishopric NH , et al.   Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3 . Proc Natl Acad Sci USA . 2002;99:12825–12830
  147. Webster KA , Graham RM , Bishopric NH . BNip3 and signal-specific programmed death in the heart . J Mol Cell Cardiol . 2005;38:35–45
  148. Imahashi K , Schneider MD , Steenbergen C , et al.   Transgenic expression of Bcl-2 modulates energy metabolism, prevents cytosolic acidification during ischemia, and reduces ischemia/reperfusion injury . Circ Res . 2004;95:734–741
  149. Vander Heiden MG , Chandel NS , Li X , et al.   Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival . Proc Natl Acad Sci USA . 2000;97:4666–4671
  150. Miccoli L , Oudard S , Sureau F , et al.   Intracellular pH governs the subcellular distribution of hexokinase in a glioma cell line . Biochem J . 1996;313:957–962
  151. Pastorino JG , Shulga N , Hoek JB . Mitochondrial binding of hexokinase II inhibits Bax-induced cytochrome c release and apoptosis . J Biol Chem . 2002;277:7610–7618
  152. Gottlob K , Majewski N , Kennedy S , et al.   Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase . Genes Dev . 2001;15:1406–1418
  153. Nicolli A , Petronilli V , Bernardi P . Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore by matrix pH. Evidence that the pore open-closed probability is regulated by reversible histidine protonation . Biochemistry . 1993;32:4461–4465
  154. Gambassi G , Hansford RG , Sollott SJ , et al.   Effects of acidosis on resting cytosolic and mitochondrial Ca2+ in mammalian myocardium . J Gen Physiol . 1993;102:575–597
  155. Kukreja RC . Essential role of oxygen radicals in delayed pharmacological preconditioning . J Mol Cell Cardiol . 2000;33:1395–1398
  156. Forbes RA , Steenbergen C , Murphy E . Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism . Circ Res . 2001;88:802–809
  157. vanden Hoek TL , Becker LB , Shao Z , et al.   Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes . J Biol Chem . 1998;273:18092–18098
  158. Dhalla NS , Temsah RM , Netticadan T . Role of oxidative stress in cardiovascular diseases . J Hypertens . 2000;18:655–673
  159. Paradies G , Petrosillo G , Pistolese M , et al.   Reactive oxygen species affect mitochondrial electron transport complex I activity through oxidative cardiolipin damage . Gene . 2002;286:135–141
  160. Petrosillo G , Ruggiero FM , Pistolese M , et al.   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 . 2001;509:435–438
  161. Malis CD , Weber PC , Leaf A , et al.   Incorporation of marine lipids into mitochondrial membranes increases susceptibility to damage by calcium and reactive oxygen species (evidence for enhanced activation of phospholipase A2 in mitochondria enriched with n-3 fatty acids) . Proc Natl Acad Sci USA . 1990;87:8845–8849
  162. Zaidi A , Michaelis ML . Effects of reactive oxygen species on brain synaptic plasma membrane Ca(2+)-ATPase . Free Radic Biol Med . 1999;27:810–821
  163. Maulik N , Yoshida T . Oxidative stress developed during open heart surgery induces apoptosis (reduction of apoptotic cell death by ebselen, a glutathione peroxidase mimic) . J Cardiovasc Pharmacol . 2000;36:601–608
  164. Szabados E , Fischer GM , Gallyas F , et al.   Enhanced ADP-ribosylation and its diminution by lipoamide after ischemia-reperfusion in perfused rat heart . Free Radic Biol Med . 1999;27:1103–1113
  165. Jain M , Cui L , Brenner DA , et al.   Increased myocardial dysfunction after ischemia-reperfusion in mice lacking glucose-6-phosphate dehydrogenase . Circulation . 2004;109:898–903
  166. Hangaishi M , Ishizaka N , Aizawa T , et al.   Induction of heme oxygenase-1 can act protectively against cardiac ischemia/reperfusion in vivo . Biochem Biophys Res Commun . 2000;279:582–588
  167. Vulapalli SR , Chen Z , Chua BHL , et al.   Cardioselective overexpression of HO-1 prevents I/R-induced cardiac dysfunction and apoptosis . Am J Physiol Heart Circ Physiol . 2002;283:H688–H694
  168. Gottlieb RA , Gruol DL , Zhu JY , et al.   Preconditioning in rabbit cardiomyocytes (role of pH, vacuolar proton ATPase, and apoptosis) . J Clin Invest . 1996;97:2391–2398
  169. Piot CA , Padmanaban D , Ursell PC , et al.   Ischemic preconditioning decreases apoptosis in rat hearts in vivo . Circulation . 1997;96:1598–1604
  170. Ding YF , Zhang MM , He RR . [Ischemic preconditioning reduces cardiomyocytic apoptosis in rabbit heart in vivo] . Sheng Li Xue Bao . 2000;52:220–224
  171. Huang JQ , Radinovic S , Rezaiefar P , et al.   In vivo myocardial infarct size reduction by a caspase inhibitor administered after the onset of ischemia . Eur J Pharmacol . 2000;402:139–142
  172. Inagaki K , Chen L , Ikeno F , et al.   Inhibition of delta-protein kinase C protects against reperfusion injury of the ischemic heart in vivo . Circulation . 2003;108:2304–2307
  173. Zhao ZQ , Corvera JS , Halkos ME , et al.   Inhibition of myocardial injury by ischemic postconditioning during reperfusion (comparison with ischemic preconditioning) . Am J Physiol Heart Circ Physiol . 2003;285:H579–H588
  174. Granville DJ , Tashakkor B , Takeuchi C , et al.   Reduction of ischemia and reperfusion-induced myocardial damage by cytochrome P450 inhibitors . Proc Natl Acad Sci USA . 2004;101:1321–1326
  175. Forbes RA , Steenbergen C , Murphy E . Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism . Circ Res . 2001;88:802–809
  176. Baines CP , Cohen MV , Downey JM . Signal transduction in ischemic preconditioning (the role of kinases and mitochondrial K(ATP) channels) . J Cardiovasc Electrophysiol . 1999;10:741–754
  177. Pain T , Yang XM , Critz SD , et al.   Opening of mitochondrial K(ATP) channels triggers the preconditioned state by generating free radicals . Circ Res . 2000;87:460–466
  178. Hausenloy DJ , Tsang A , Mocanu MM , et al.   Ischemic preconditioning protects by activating prosurvival kinases at reperfusion . Am J Physiol Heart Circ Physiol . 2005;288:H971–H976
  179. Murphy E . Primary and secondary signaling pathways in early preconditioning that converge on the mitochondria to produce cardioprotection . Circ Res . 2004;94:7–16
  180. Guo Y , Jones WK , Xuan YT , et al.   The late phase of ischemic preconditioning is abrogated by targeted disruption of the inducible NO synthase gene . Proc Natl Acad Sci USA . 1999;96:11507–11512
  181. Vondriska TM , Zhang J , Song C , et al.   Protein kinase C epsilon-Src modules direct signal transduction in nitric oxide-induced cardioprotection (complex formation as a means for cardioprotective signaling) . Circ Res . 2001;88:1306–1313
  182. Wang G , Liem DA , Vondriska TM , et al.   Nitric oxide donors protect the murine myocardium against infarction via modulation of mitochondrial permeability transition . Am J Physiol Heart Circ Physiol . 2005;288(3):H1290–H1295
  183. Qin Q , Yang XM , Cui L , et al.   Exogenous NO triggers preconditioning via a cGMP- and mitoKATP-dependent mechanism . Am J Physiol Heart Circ Physiol . 2004;287:H712–H718
  184. Xu Z , Ji X , Boysen PG . Exogenous nitric oxide generates ROS and induces cardioprotection (involvement of PKG, mitochondrial KATP channels, and ERK) . Am J Physiol Heart Circ Physiol . 2004;286:H1433–H1440
  185. Ytrehus K , Liu Y , Downey JM . Preconditioning protects ischemic rabbit heart by protein kinase C activation . Am J Physiol . 1994;35:H1145–H1152
  186. Baxter GF , Goma FM , Yellon DM . Involvement of protein kinase C in the delayed cytoprotection following sublethal ischaemia in rabbit myocardium . Br J Pharmacol . 1995;115:222–224
  187. Liu GS , Cohen MV , Mochly-Rosen D , et al.   Protein kinase C-epsilon is responsible for the protection of preconditioning in rabbit cardiomyocytes . J Mol Cell Cardiol . 1999;31:1937–1948
  188. Hahn HS , Yussman MG , Toyokawa T , et al.   Ischemic protection and myofibrillar cardiomyopathy (dose-dependent effects of in vivo δPKC inhibition) . Circ Res . 2002;91:741–748
  189. Baines CP , Zhang J , Wang GW , et al.   Mitochondrial PKCϵ and MAPK form signaling modules in the murine heart (enhanced mitochondrial PKCϵ-MAPK interactions and differential MAPK activation in PKCϵ-induced cardioprotection) . Circ Res . 2002;90:390–397
  190. Bouwman RA , Musters RJ , Beek-Harmsen BJ , et al.   Reactive oxygen species precede protein kinase C-delta activation independent of adenosine triphosphate-sensitive mitochondrial channel opening in sevoflurane-induced cardioprotection . Anesthesiology . 2004;100:506–514
  191. Das A , Ockaili R , Salloum F , et al.   Protein kinase C plays an essential role in sildenafil-induced cardioprotection in rabbits . Am J Physiol Heart Circ Physiol . 2004;286:H1455–H1460
  192. Rybin VO , Guo J , Sabri A , et al.   Stimulus-specific differences in protein kinase Cδ localization and activation mechanisms in cardiomyocytes . J Biol Chem . 2004;279:19350–19361
  193. Rybin VO , Sabri A , Short J , et al.   Cross-regulation of novel protein kinase C (PKC) isoform function in cardiomyocytes . J Biol Chem . 2003;278:14555–14564
  194. Fryer RM , Wang Y , Hsu AK , et al.   Essential activation of PKC-delta in opioid-initiated cardioprotection . Am J Physiol Heart Circ Physiol . 2001;280:H1346–H1353
  195. Zhao TC , Kukreja RC . Protein kinase C-delta mediates adenosine A3 receptor-induced delayed cardioprotection in mouse . Am J Physiol Heart Circ Physiol . 2003;285:H434–H441
  196. Harada N , Miura T , Dairaku Y , et al.   NO donor-activated PKC-delta plays a pivotal role in ischemic myocardial protection through accelerated opening of mitochondrial K-ATP channels . J Cardiovasc Pharmacol . 2004;44:35–41
  197. Murriel CL , Churchill E , Inagaki K , et al.   [title]Protein kinase Cδ activation induces apoptosis in response to cardiac ischemia and reperfusion damage . J Biol Chem . 2004;279:47985–47991
  198. Ilangovan G , Osinbowale S , Bratasz A , et al.   Heat shock regulates the respiration of cardiac H9c2 cells through upregulation of nitric oxide synthase . AJP Cell Physiol . 2004;287:C1472–C1481
  199. Walford GA , Moussignac RL , Scribner AW , et al.   Hypoxia potentiates nitric oxide-mediated apoptosis in endothelial cells via peroxynitrite-induced activation of mitochondria-dependent and -independent pathways . J Biol Chem . 2004;279:4425–4432
  200. Cooper CE , Davies NA , Psychoulis M , et al.   Nitric oxide and peroxynitrite cause irreversible increases in the K(m) for oxygen of mitochondrial cytochrome oxidase (in vitro and in vivo studies) . Biochim Biophys Acta . 2003;1607:27–34
  201. Jones SP , Greer JJ , Kakkar AK , et al.   Endothelial nitric oxide synthase overexpression attenuates myocardial reperfusion injury . Am J Physiol Heart Circ Physiol . 2004;286:H276–H282
  202. Wang P , Chen H , Qin H , et al.   Overexpression of human copper, zinc-superoxide dismutase (SOD1) prevents postischemic injury . Proc Natl Acad Sci USA . 1998;95:4556–4560
  203. Chen Z , Siu B , Ho YS , et al.   Overexpression of MnSOD protects against myocardial ischemia/reperfusion injury in transgenic mice . J Mol Cell Cardiol . 1998;30:2281–2289
  204. Cuzzocrea S , Mazzon E , Dugo L , et al.   Superoxide (a key player in hypertension) . FASEB J . 2004;18:94–101
  205. Zhao M , Chen Y , Li Y . [Changes of apoptosis and Fas gene expression in cardiomyocytes of rats with myocardial reperfusion and the effects of ischemic preconditioning] . Zhonghua Nei Ke Za Zhi . 1999;38:753–756
  206. Lecour S , Rochette L , Opie L . Free radicals trigger TNFalpha-induced cardioprotection . Cardiovasc Res . 2005;65:239–243
  207. Zhang DX , Fryer RM , Hsu AK , et al.   Production and metabolism of ceramide in normal and ischemic-reperfused myocardium of rats . Basic Res Cardiol . 2001;96:267–274
  208. Tepper CG , Jayadev S , Liu B , et al.   Role for ceramide as an endogenous mediator of Fas-induced cytotoxicity . Proc Natl Acad Sci USA . 1995;92:8443–8447
  209. Mathias S , Dressler KA , Kolesnick RN . Characterization of a ceramide-activated protein kinase (stimulation by tumor necrosis factor α) . Proc Natl Acad Sci USA . 1991;88:10009–10013
  210. Schulze-Osthoff K , Bakker AC , Vanhaesebroeck B , et al.   Cytotoxic activity of tumor necrosis factor is mediated by early damage of mitochondrial functions . J Biol Chem . 1992;267:5317–5323
  211. Birbes H , El Bawab S , Hannun YA , et al.   Selective hydrolysis of a mitochondrial pool of sphingomyelin induces apoptosis . FASEB J . 2001;15:2669–2679
  212. Arora AS , Jones BJ , Patel TC , et al.   Ceramide induces hepatocyte cell death through disruption of mitochondrial function in the rat . Hepatology . 1997;25:958–963
  213. Argaud L , Prigent AF , Chalabreysse L , et al.   Ceramide in the antiapoptotic effect of ischemic preconditioning . Am J Physiol Heart Circ Physiol . 2004;286:H246–H251
  214. Jarvis WD , Fornari FA , Browning JL , et al.   Attenuation of ceramide-induced apoptosis by diglyceride in human myeloid leukemia cells . J Biol Chem . 1994;269:31685–31692
  215. Weiss JN , Korge P , Honda HM , et al.   Role of the mitochondrial permeability transition in myocardial disease . Circ Res . 2003;93:292–301
  216. Gottlieb RA . Mitochondrial signaling in apoptosis (mitochondrial daggers to the breaking heart) . Basic Res Cardiol . 2003;98:242–249
  217. Piot CA , Martini JF , Bui SK , et al.   Ischemic preconditioning attenuates ischemia/reperfusion-induced activation of caspases and subsequent cleavage of poly(ADP-ribose) polymerase in rat hearts in vivo . Cardiovasc Res . 1999;44:536–542
  218. Korge P , Honda HM , Weiss JN . Protection of cardiac mitochondria by diazoxide and protein kinase C (implications for ischemic preconditioning) . Proc Natl Acad Sci USA . 2002;99:3312–3317
  219. Nakamura M , Wang NP , Zhao ZQ , et al.   Preconditioning decreases Bax expression, PMN accumulation and apoptosis in reperfused rat heart . Cardiovasc Res . 2000;45:661–670
  220. Uchiyama T , Engelman RM , Maulik N , et al.   Role of Akt signaling in mitochondrial survival pathway triggered by hypoxic preconditioning . Circulation . 2004;109:3042–3049
  221. LaDisa JF , Krolikowski JG , Pagel PS , et al.   Cardioprotection by glucose-insulin-potassium (dependence on KATP channel opening and blood glucose concentration before ischemia) . Am J Physiol Heart Circ Physiol . 2004;287:H601–H607
  222. Huang TJ , Verkhratsky A , Fernyhough P . Insulin enhances mitochondrial inner membrane potential and increases ATP levels through phosphoinositide 3-kinase in adult sensory neurons . Mol Cell Neurosci . 2005;28:42–54
  223. Huang J , Ito Y , Morikawa M , et al.   Bcl-xL gene transfer protects the heart against ischemia/reperfusion injury . Biochem Biophys Res Commun . 2003;311:64–70
  224. Ono M , Sawa Y , Ryugo M , et al.   BH4 peptide derivative from Bcl-xL attenuates ischemia/reperfusion injury thorough anti-apoptotic mechanism in rat hearts . Eur J Cardiothorac Surg . 2005;27:117–121
  225. Gustafsson AB , Tsai JG , Logue SE , et al.   ARC protects against cell death by interfering with Bax activation . J Biol Chem . 2004;273:21233–21238
  226. Argaud L , Gateau-Roesch O , Chalabreysse L , et al.   Preconditioning delays Ca2+-induced mitochondrial permeability transition . Cardiovasc Res . 2004;61:115–122
  227. Murata M , Akao M , O’Rourke B , et al.   Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion (possible mechanism of cardioprotection) . Circ Res . 2001;89:891–898
  228. Ishida H , Hirota Y , Genka C , et al.   Opening of mitochondrial K(ATP) channels attenuates the ouabain-induced calcium overload in mitochondria . Circ Res . 2001;89:856–858
  229. Wang L , Cherednichenko G , Hernandez L , et al.   Preconditioning limits mitochondrial Ca(2+) during ischemia in rat hearts (role of K(ATP) channels) . Am J Physiol Heart Circ Physiol . 2001;280:H2321–H2328
  230. Holmuhamedov EL , Wang L , Terzic A . ATP-sensitive K+ channel openers prevent Ca2+ overload in rat cardiac mitochondria . J Physiol (Lond) . 1999;519:347–360
  231. Griffiths EJ , Halestrap AP . Protection by Cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts . J Mol Cell Cardiol . 1993;25:1461–1469
  232. Di Lisa F , Menabo R , Canton M , et al.   Opening of the mitochondrial permeability transition pore causes depletion of mitochondrial and cytosolic NAD+ and is a causative event in the death of myocytes in post-ischemic reperfusion of the heart . J Biol Chem . 2000;276:2571–2575
  233. Hausenloy DJ , Duchen MR , Yellon DM . Inhibiting mitochondrial permeability transition pore opening at reperfusion protects against ischaemia-reperfusion injury . Cardiovasc Res . 2003;60:617–625
  234. Lim KHH , Javadov SA , Das M , et al.   The effects of ischaemic preconditioning, diazoxide and 5-hydroxydecanoate on rat heart mitochondrial volume and respiration . J Physiol (Lond) . 2002;545:961–974
  235. Hausenloy D , Wynne A , Duchen M , et al.   Transient mitochondrial permeability transition pore opening mediates preconditioning-induced protection . Circulation . 2004;109:1714–1717
  236. Crompton M , Virji S , Ward JM . Cyclophilin-D binds strongly to complexes of the voltage-dependent anion channel and the adenine nucleotide translocase to form the permeability transition pore . Eur J Biochem . 1998;258:729–735
  237. Halestrap AP , Kerr PM , Javadov S , et al.   Elucidating the molecular mechanism of the permeability transition pore and its role in reperfusion injury of the heart . Biochim Biophys Acta . 1998;1366:79–94
  238. Marzo I , Brenner C , Zamzami N , et al.   Bax and adenine nucleotide translocator cooperate in the mitochondrial control of apoptosis . Science . 1998;281:2027–2031
  239. Fontaine E , Bernardi P . Progress on the mitochondrial permeability transition pore (regulation by complex I and ubiquinone analogs) . J Bioenerg Biomembr . 1999;31:335–345
  240. Brady NR , Elmore SP , van Beek JJHG , et al.   Coordinated behavior of mitochondria in both space and time (a reactive oxygen species-activated wave of mitochondrial depolarization) . Biophys J . 2004;87:2022–2034
  241. Precht TA , Phelps RA , Linseman DA , et al.   The permeability transition pore triggers Bax translocation to mitochondria during neuronal apoptosis . Cell Death Differ . 2005;12:1–11
  242. Lim ML , Minamikawa T , Nagley P . The protonophore CCCP induces mitochondrial permeability transition without cytochrome c release in human osteosarcoma cells . FEBS Lett . 2001;503:69–74
  243. Iwamoto H , Miura T , Okamura T , et al.   Calpain inhibitor-1 reduces infarct size and DNA fragmentation of myocardium in ischemic/reperfused rat heart . J Cardiovasc Pharmacol . 1999;33:580–586
  244. Werneburg N , Guicciardi ME , Yin XM , et al.   TNF-alpha-mediated lysosomal permeabilization is FAN and caspase 8/Bid dependent . Am J Physiol Gastrointest Liver Physiol . 2004;287:G436–G443
  245. Broker LE , Huisman C , Span SW , et al.   Cathepsin B mediates caspase-independent cell death induced by microtubule stabilizing agents in non-small cell lung cancer cells . Cancer Res . 2004;64:27–30
  246. Ichihara K , Hayase N , Chiba K , et al.   Effect of NCO-700, an inhibitor of protease, on lysosomal rupture in the ischemic myocardium . J Pharm Sci . 1991;80:252–254
  247. Pye J , Ardeshirpour F , McCain A , et al.   Proteasome inhibition ablates activation of NF-kappa B in myocardial reperfusion and reduces reperfusion injury . Am J Physiol Heart Circ Physiol . 2003;284:H919–H926
  248. Campbell B , Adams J , Shin YK , et al.   Cardioprotective effects of a novel proteasome inhibitor following ischemia and reperfusion in the isolated perfused rat heart . J Mol Cell Cardiol . 1999;31:467–476
  249. Lindsey ML . MMP induction and inhibition in myocardial infarction . Heart Fail Rev . 2004;9:7–19
  250. Kloner RA , Bolli R , Marban E , et al.   Medical and cellular implications of stunning, hibernation, and preconditioning (an NHLBI workshop) . Circulation . 1998;97(18):1848–1867 (May 12)
  251. Cigarroa CG , deFilippi CR , Brickner ME , et al.   Dobutamine stress echocardiography identifies hibernating myocardium and predicts recovery of left ventricular function after coronary revascularization . Circulation . 1993;88(2):430–436 (Aug)
  252. Topol EJ , Weiss JL , Guzman PA , et al.   Immediate improvement of dysfunctional myocardial segments after coronary revascularization (detection by intraoperative transesophageal echocardiography) . J Am Coll Cardiol . 1984;4(6):1123–1134 (Dec)
  253. Maes A , Flameng W , Nuyts J , et al.   Histological alterations in chronically hypoperfused myocardium. Correlation with PET findings . Circulation . 1994;90(2):735–745 (Aug)
  254. Ausma J , Cleutjens J , Thone F , et al.   Chronic hibernating myocardium (interstitial changes) . Mol Cell Biochem . 1995;147(1-2):35–42 (Jun 7-21)
  255. Chen C , Ma L , Linfert DR , et al.   Myocardial cell death and apoptosis in hibernating myocardium . J Am Coll Cardiol . 1997;30(5):1407–1412 (Nov 1)
  256. Lim H , Fallavollita JA , Hard R , et al.   Profound apoptosis-mediated regional myocyte loss and compensatory hypertrophy in pigs with hibernating myocardium . Circulation . 1999;100(23):2380–2386 (Dec 7)
  257. Elsasser A , Schlepper M , Klovekorn WP , et al.   Hibernating myocardium (an incomplete adaptation to ischemia) . Circulation . 1997;96(9):2920–2931 (Nov 4)
  258. Elsasser A , Vogt AM , Nef H , et al.   Human hibernating myocardium is jeopardized by apoptotic and autophagic cell death . J Am Coll Cardiol . 2004;43(12):2191–2199
  259. Dispersyn GD , Ausma J , Thone F , et al.   Cardiomyocyte remodelling during myocardial hibernation and atrial fibrillation (prelude to apoptosis) . Cardiovasc Res . 1999;43(4):947–957 (Sep)
  260. Schwarz ER , Schoendube FA , Kostin S , et al.   Prolonged myocardial hibernation exacerbates cardiomyocyte degeneration and impairs recovery of function after revascularization . J Am Coll Cardiol . 1998;31(5):1018–1026 (Apr)
  261. Mauney M , Kron I . The physiologic basis of warm cardioplegia . Ann Thorac Surg . 1995;60:819–823
  262. Schmitt JP , Schroder J , Schunkert H , et al.   Role of apoptosis in myocardial stunning after open heart surgery . Ann Thorac Surg . 2002;73(4):1229–1235
  263. Chen Y , Wu S , Huang C , et al.   Morphometric identification of luminal narrowing of myocardial capillaries after cardioplegic arrest . Ann Thorac Surg . 2001;71:243–248
  264. Rainio P , Kaukoranta P , Sormunen R , et al.   Ultrastructural changes in myocardium during mild hypothermic retrograde blood cardioplegia . Scand Cardiovasc J . 1998;32:353–359
  265. Aebert H , Kirchner S , Keyser A , et al.   Induction of early immediate genes and programmed cell death following cardioplegic arrest in human hearts . Eur J Cardiothorac Surg . 2000;18:589–593
  266. Lawrence K , Chanalaris A , Scarabelli TM , et al.   KATP channel gene expression is induced by urocortin and mediates its cardioprotective effect . Circulation . 2002;106(12):1556–1562
  267. Green DR . Apoptotic pathways (the roads to ruin) . Cell . 1998;94(6):695–698
  268. Fisher UM , Tossios P , Huebner A , et al.   Myocardial apoptosis prevention by radical scavenging in patients undergoing cardiac surgery . J Thorac Cardiovasc Surg . 2004;128(1):103–108
  269. Singh K , Xiao L , Remondino A , et al.   Adrenergic regulation of cardiac myocyte apoptosis . J Cell Physiol . 2001;189(3):257–265
  270. Communal C , Sumandea M , de Tombe P , et al.   Functional consequences of caspase activation in cardiac myocytes . Proc Natl Acad Sci USA . 2002;99(9):6252–6256
  271. Chen-Scarabelli C , Hughes S , Landon G , et al.   A case of fatal ephedra intake associated with lipofuscin accumulation, caspase activation and cleavage of myofibrillary proteins . Eur J Heart Failure . 2005; (in press).
  272. Mukherjee R , Yarbrough WM , Reese ES , et al.   Myocyte contractility with caspase inhibition and simulated hyperkalemic cardioplegic arrest . Ann Thorac Surg . 2004;77(5):1684–1689
  273. Tetracyclines. The Merck Manual. Section 13—Infectious Diseases, Chapter 153—Antibacterial drugs. Accessed at http://www.merck.com/mrkshared/mmanual/section13/chapter153/153e.jsp on 4/13/04.
  274. Minocycline. Accessed at http://www.medscape.com/druginfo on 4/13/04.
  275. Yrjanheikki J , Tikka T , Goldsteins G , et al.   A tetracycline derivate, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window . Proc Natl Acad Sci USA . 1999;96:13496–13500
  276. Yrjanheikki J , Keinanen R , Pellikka M , et al.   Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia . Proc Natl Acad Sci USA . 1998;95:15769–15774
  277. Rothwell NJ , Loddick SA , Stroemer P . Interleukins and cerebral ischaemia . Int Rev Neurobiol . 1997;40:281–298
  278. Chen M , Ona VO , Li M , et al.   Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease . Nat Med . 2000;6:797–801
  279. Wang X , Zhu S , Drozda M , et al.   Minocycline inhibits caspase-independent and -dependent mitochondrial cell death pathways in models of Huntington’s disease . Proc Natl Acad Sci USA . 2003;100:10483–10487
  280. Du Y , Ma Z , Lin S , et al.   Minocycline prevents nigrostriatal dopaminergic neurodegeneration in the MPTP model of Parkinson’s disease . Proc Natl Acad Sci USA . 2001;98:14669–14674
  281. Zhu S , Stavrovskaya IG , Drozda M , et al.   Minocycline inhibits cytochrome c release and delays progression of amyotrophic lateral sclerosis in mice . Nature . 2002;417:74–78
  282. Van Den Bosch L , Tilkin P , Lemmens G , et al.   Minocycline delays disease onset and mortality in a transgenic model of ALS . Neuroreport . 2002;13:1067–1070
  283. Lee SM , Yune TY , Kim SJ , et al.   Minocycline reduces cell death and improves functional recovery after traumatic spinal cord injury in the rat . J Neurotrauma . 2003;20:1017–1027
  284. Wang J , Wei Q , Wang CY , et al.   Minocycline up-regulates Bcl-2 and protects against cell death in the mitochondria . J Biol Chem . 2004;279:19948–19954
  285. Matsuki S , Iuchi Y , Ikeda Y , et al.   Suppression of cytochrome c release and apoptosis in testes with heat stress by minocycline . Biochem Biophys Res Commun . 2003;312:843–849
  286. Habib KE , Gold PW , Chrousos GP . Neuroendocrinology of stress . Endocrinol Metab Clin North Am . 2001;30:695–728
  287. Tsigos C , Chrausos GP . J. Hypothalamic-pituitary—adrenal axis, neuroendocrine factors and stress . Psychosome Res . 2002;53:865–871
  288. Vale WW , Spiess J , Rivier C , et al.   Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin . Science . 1981;213:1394–1397
  289. Muglia LJ , Jenkins NA , Gilbert DJ , et al.   Expression of the mouse corticotropin-releasing hormone gene in vivo and targeted inactivation in embryonic stem cells . J Clin Invest . 1994;93:2066–2067
  290. Lovejoy DA , Balment RJ . Evolution and physiology of the corticotropin-releasing factor (CRF) family of neuropeptides in vertebrates . Gen Comp Endocrinol . 1999;115:1–22
  291. Vaughan J , Donaldson C , Bittencourt J , et al.   Urocortin, a mammalian neuropeptide related to fish urotensin I and to corticotropin-releasing factor . Nature . 1995;378:287–292
  292. Reyes TM , Lewis K , Perrin MH , et al.   Urocortin II (a member of the corticotropin-releasing factor (CRF) neuropeptide family that is selectively bound by type 2 CRF receptors) . Proc Natl Acad Sci USA . 2001;98:2843–2848
  293. Hsu SY , Hsueh AJ . Human stresscopin and stresscopin-related peptide are selective ligands for the type 2 corticotropin-releasing hormone receptor . Nat Med . 2001;7:605–611
  294. Lewis K , Li C , Perrin MH , et al.   Identification of urocortin III, an additional member of the corticotropin-releasing factor (CRF) family with high affinity for the CRF2 receptor . Proc Natl Acad Sci USA . 2001;98: 757–5
  295. Donaldson CJ , Sutton DW , Perrin MH , et al.   Cloning and characterization of human urocortin . Endocrinology . 1996;137:2167–2170
  296. Hillhouse EW , Randerva H , Ladds G , et al.   Corticotropin-releasing hormone receptors . Biochem Soc Trans . 2002;30:428–432
  297. Coste SC , Quiontos RF , Stenzel-Poor MP . Corticotropin-releasing hormone-related peptides and receptors (emergent regulators of cardiovascular adaptations to stress) . Trends Cardiovasc Med . 2002;12:176–182
  298. Chen R , Lewis KA , Perrin MH , et al.   Expression cloning of a human corticotropin-releasing-factor receptor . Proc Nat Acad Sci USA . 1993;90:8967–8971
  299. Perrin MH , Donaldson CJ , Chen R , et al.   Cloning and functional expression of a rat brain corticotropin releasing factor (CRF) receptor . Endocrinology . 1993;133:3058–3061
  300. Lovenberg TW , Liaw CW , Grigoriadis DE , et al.   Cloning and characterization of a functionally distinct corticotropin-releasing factor receptor subtype from rat brain . Proc Natl Acad Sci USA . 1995;92:836–840
  301. Blank T , Nilholt L , Grammatopoulos DK , et al.   Corticotropin-releasing factor receptors couple to multiple G-proteins to activate diverse intracellular signaling pathways in mouse hippocampus (role in neuronal excitability and associative learning) . J Neurosci . 2003;23:700–707
  302. Karteris E , Grammatopoulos DK , Randeva H , et al.   Signal transduction characteristics of the corticotropin-releasing hormone receptors in the feto-placental unit . J Clin Endocrinol Metab . 2000;85:1989–1996
  303. Dautzenberg FM , Mevenkamp G , Wille S , et al.   N-terminal splice variants of the type I PACAP receptor (isolation, characterization and ligand binding/selectivity determinants) . Neuroendocrinology . 1999;12:941–949
  304. Okosi A , Brar BK , Chan M , et al.   Expression and protective effects of urocortin in cardiac myocytes . Neuropeptides . 1998;32:167–171
  305. Brar BK , Stephanou A , Okosi A , et al.   H-like peptides protect cardiac myocytes from lethal schaemic injury . Mol Cell Endocrinol . 1999;158:55–63
  306. Latchman DS . Urocortin International . J Biochem Cell Biol . 2002;34:907–910
  307. Latchman DS . Urocortin protects against ischaemic injury via a MAPK-dependent pathway . Trends Cardivasc Med . 2001;11:167–169
  308. Brar BK , Jonassen AK , Stephanou AS , et al.   Urocortin protects against ischemic and reperfusion injury via a MAP-kinase dependent pathway . J Biol Chem . 2000;275:8508–8514
  309. Brar BK , Stephanou AS , Knight RA , et al.   Activation of protein kinase B/Akt by Urocortin is essential for its ability to protect cardiac cells against hypoxia/reoxygenation-induced cell death . J Mol Cell Cardiol . 2002;34:483–492
  310. Schulman D , Latchman DS , Yellon DM . Urocortin protects the heart from reperfusion injury via upregulation of p42/p44 MAPK signaling pathway Am J Physiol Heart Circ Physiol . 2002;283:H1481–H1488
  311. Chanalaris A , Lawrence KM , Stephanou A , et al.   Protective effects of the urocortin homologues stresscopin (SCP) and stresscopin-related peptide (SRP) against hypoxia/reoxygenation injury in rat neonatal cardiomyocytes . J Mol Cell Cardiol . 2003;25:1295–1305
  312. Brar BK , Jonassen AK , Egorina EM , et al.   Urocortin-II and urocortin-III are cardioprotective against ischemia reperfusion injury (an essential endogenous cardioprotective role for corticotropin releasing factor receptor type 2 in the murine heart) . Endocrinology . 2004;145:24–35
  313. Naruse K , King GL . Protein kinase C and myocardial biology and function . Circ Res . 2000;86:1104–1110
  314. Mackay K , Mochly-Rosen D . Localization, anchoring, and functions of protein kinase C isozymes in the heart . Mol Cell Cardiol . 2001;33:1301–1307
  315. Mochly-Rosen D . Localization of protein kinases by anchoring proteins (a theme in signal transduction) . Science . 1995;268:247–251
  316. Souroujon MC , Mochly-Rosen D . Peptide modulators of protein-protein interactions in intracellular signaling . Nat Biotechnol . 1998;110:919–924
  317. Chen L , Wright R , Chen H , et al.   Molecular transporters for peptides (delivery of a cardioprotective epsilon PKC agonist peptide into cells and intact ischaemic heart using a transport system) . R. Chem Biol . 2001;8:1123–1129
  318. Murriel C , Mochly-Rosen D . Opposing roles of δ and ϵ PKC in cardiac ischemia and reperfusion (targeting the apoptotic machinery) . Arch Biochem Biophys . 2003;420:246–254
  319. Sargent CA , Sleph PG , Dzwonczyk S , et al.   Effect of calmodulin and protein kinase C inhibitors on globally ischemic rat hearts . J Cardiovasc Pharmacol . 1992;20:251–260
  320. Disatnik MH , Buraggi G , Mochly-Rosen D . Localization of protein kinase C isozymes in cardiac myocytes . Exp Cell Res . 1994;210:287–297
  321. Jin ZQ , Zhou HZ , Zhu P , et al.   Cardioprotection mediated by sphingosine-1-phosphate and ganglioside GM-1 in wild-type and PKC epsilon knockout mouse hearts . Am J Physiol Heart Circ Physiol . 2002;282(6):H1970
  322. Saurin AT , Pennington DJ , Nicolaas JH , et al.   Targeted disruption of the Protein Kinase C epsilon gene abolishes the infarct size reduction that follows ischaemic preconditioning of isolated buffer-perfused mouse hearts . Cardiovas Res . 2002;55:672–680
  323. Liu GS , Cohen MV , Mochly-Rosen D , et al.   Protein kinase C-ϵ is responsible for the protection of preconditioning in rabbit cardiomyocytes . J Mol Cardiol . 1999;31:1937–1948
  324. Przyklenk K , Sussman MA , Simkhovich BZ , et al.   Does ischemic preconditioning trigger translocation of protein kinase C in the canine model? . Circulation . 1995;92:1546–1557
  325. Lawrence KM , Kabir AMN , Bellahcene M , et al.   Cardioprotection mediated by urocortin is dependent upon PKCϵ activation . FASEB J . 2005; (in press).
  326. Tao J , Xu H , Yang C , et al.   Effect of urocortin on L-type calcium currents in adult rat ventricular myocytes . Pharmacol Res . 2004;47:1–6
  327. Brar BK , Railson J , Stephanou AS , et al.   Urocortin increases the expression of heat shock protein 90 in rat cardiac myocytes in a MEK 1/2-dependent manner . J Endocrinol . 2002;172:283–293
  328. Latchman DS . Cardiotrophin-1 (CT-1) (a novel hypertrophic and cardioprotective agent) . J Exp Pathol . 1999;80:189–196
  329. Janjua S , Lawrence KM , Ng LL , et al.   The cardioprotective agent urocortin induces expression of CT . Cardiovasc Toxicol . 2003;3:255–262
  330. Lawrence KM , Chanalaris  , Scarabelli T , et al.   KATP channel gene expression is induced by urocortin and mediates its cardioprotective effect . Circulation . 2002;106:1556–1562
  331. Noma A . ATP-regulated K+ channels in cardiac myocytes . Nature . 1983;305:147–148
  332. Gross G . ATP-sensitive potassium channels and myocardial preconditioning . Basic Res Cardiol . 1995;90:85–88
  333. Cole W , McPherson C , Sontag D . ATP-regulated K+ channels protect the myocardium against ischemia/reperfusion damage . Circ Res . 1991;69:571–581
  334. O’Rourke B . Myocardial Katp channels in preconditioning . Circ Res . 2000;87:845–855
  335. Takano H , Tang X-L , Bolli R . Differential role of KATP channels in late preconditioning against myocardial stunning and infarction in rabbits . Am J Physiol Heart Circ Physiol . 2000;279:H2350–H2359
  336. Suzuki M , Kotake K , Fujikura K , et al.   Kir 6.1 a possible subunit of ATP sensitive K+ channels . Biochem Biophys Res Commun . 1997;241:693–697
  337. Inagaki N , Tsuura Y , Namba N , et al.   Cloning and functional characterisation of a novel ATP-sensitive potassium channel ubiquitously expressed in rat tissues, including pancreatic islets, pituitary, skeletal muscle and heart . J Biol Chem . 1995;270:5691–5694
  338. Seino S . ATP-sensitive potassium channels (a model of heteromultimeric potassium channel/receptor assemblies) . Annu Rev Physiol . 1999;6:337–362
  339. Seharaseyon J , Ohler A , Sasaki N , et al.   Molecular composition of mitochondrial ATP-sensitive potassium channels probed by viral Kir gene transfer . J Mol Cell Cardiol . 2000;32:1923–1930
  340. Cummings BS , Mchowat J , Schnellmann RG . Phospholipase A2s in cell death and injury . J Pharmacol Exp Ther . 2000;294:793–799
  341. Daleau P . Lysophosphatidylcholine, a metabolite which accumulates early in myocardium during ischaemia, reduces gap junction coupling in cardiac cells . J Mol Cell Cardiol . 1999;31:1391–1401
  342. Shizume H , Hoque AN , Magishi K , et al.   A new approach to the development of anti-ischaemic drugs. Substances that counteract the deleterious effect of lysophosphatidylcholine . Jpn Heart J . 1997;38:11–25
  343. Lawrence KM , Scarabelli TM , Turtle L , et al.   Urocortin protects cardiac myocytes from ischemia/reperfusion injury by attenuating calcium-insensitive phospholipase A2 gene expression . FASEB J . 2003;15:2313–2315
  344. Ferri KF , Kroemer G . Organelle specific initiation of cell death pathways . Nat Cell Biol . 2001;3:E255–E263
  345. Levraut J , Iwase H , Shao ZH , et al.   Cell death during ischaemia (relationship to mitochondrial depolarisation and ROS generation) . Am J Physiol Heart Circ Physiol . 2003;284:H549–H558
  346. Borutaite V , Brown GC . Mitochondria in apoptosis of ischaemic heart . FEBS Lett . 2003;54:1–5
  347. Williams SD , Gottlieb RA . Inhibition of mitochondrial calcium-independent phospholipase A2 (iPLA2) attenuates mitochondrial phospholipid loss and is cardioprotective . Biochem J . 2002;362:23–32
  348. Lawrence KM , Townsend PA , Davidson SM , et al.   The cardioprotective effect of urocortin during ischaemia/reperfusion involves the prevention of mitochondrial damage . Biochem Biophys Res Commun . 2004;321:479–486
  349. Lunbaek JA , Andersen OS . Lysophospholipids modulate channel function by altering the mechanical properties of lipid bilayers . J Gen Physiol . 1994;104:645–673
  350. Eddlestone GT . ATP-sensitive K channel modulation by products of PLA2 in the insulin-secreting HIT cell line . Am J Physiol . 1995;268:C181
  351. Steer SA , Wirsig KC , Creer H , et al.   Regulation of membrane-associated iPLA2 activity by a novel PKC isoform in ventricular myocytes . Am J Cell Physiol . 2000;238:1621–1626
  352. Sato T , O’Rourke B , Marban E . Modulation of mitochondrial ATP-dependent K+ channels by protein kinase C . Circ Res . 1998;83:110–114
  353. Numa Y , Miura T , Miki T , et al.   Opening of mitochondrial K(ATP) channel occurs downstream of PKC-epsilon activation in the mechanism of preconditioning . Am J Physiol Heart Circ Physiol . 2002;283(1):H440–H447
  354. Wang Y , Ashraf M . Role of protein kinase C in mitochondrial KATP channel-mediated protection against Ca2+ overload injury in rat myocardium . Circ Res . 1999;84:1156–1165
  355. Baines P , Song C-X , Zhen Y-T , et al.   Protein kinase Cϵ interacts with and inhibits the permeability transition pore in cardiac mitochondria . Circ Res . 2003;92:873–880
  356. Ping P , Zhang J , Pierce WM , et al.   Functional proteomic analysis of protein kinase C epsilon signaling complexes in the normal heart and during cardioprotection . Circ Res . 2001;88:59–62

 The authors have no conflicts of interest to disclose.

PII: S0146-2806(05)00175-1

doi: 10.1016/j.cpcardiol.2005.11.002

Current Problems in Cardiology
Volume 31, Issue 3 , Pages 181-264 , March 2006