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01-03-2009 | Review

The mitochondrial permeability transition pore as a target for preconditioning and postconditioning

Authors: Derek J. Hausenloy, Sang-Bing Ong, Derek M. Yellon

Published in: Basic Research in Cardiology | Issue 2/2009

Abstract

The experimental evidence supporting the mitochondrial permeability transition pore (mPTP) as a major mediator of lethal myocardial reperfusion injury and therefore a critical target for cardioprotection is persuasive. Although, its molecular identity eludes investigators, it is generally accepted that mitochondrial cyclophilin-D, the target for the inhibitory effects of cyclosporine-A on the mPTP, is a regulatory component of the mPTP. Animal myocardial infarction studies and a recent clinical proof-of-concept study have demonstrated that pharmacologically inhibiting its opening at the onset of myocardial reperfusion reduces myocardial infarct size in the region of 30–50%. Interestingly, the inhibition of mPTP opening at this time appears to underpin the infarct-limiting effects of the endogenous cardioprotective strategies of ischemic preconditioning (IPC) and postconditioning (IPost). However, the mechanism underlying this inhibitory action of IPC and IPost on mPTP opening is unclear. The objectve of this review article will be to explore the potential mechanisms which link IPC and IPost to mPTP inhibition in the reperfused heart.

Abdallah Y, Gkatzoflia A, Gligorievski D, Kasseckert S, Euler G, Schluter KD, Schafer M, Piper HM, Schafer C (2006) Insulin protects cardiomyocytes against reoxygenation-induced hypercontracture by a survival pathway targeting SR Ca²⁺ storage. Cardiovasc Res 70:346–353PubMedCrossRef

Ahmad N, Wang Y, Haider KH, Wang B, Pasha Z, Uzun O, Ashraf M (2006) Cardiac protection by mitoKATP channels is dependent on Akt translocation from cytosol to mitochondria during late preconditioning. Am J Physiol Heart Circ Physiol 290:H2402–H2408PubMedCrossRef

Andrukhiv A, Costa AD, West IC, Garlid KD (2006) Opening mitoKATP increases superoxide generation from complex I of the electron transport chain. Am J Physiol Heart Circ Physiol 291:H2067–H2074PubMedCrossRef

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

Argaud L, Gateau-Roesch O, Augeul L, Couture-Lepetit E, Loufouat J, Gomez L, Robert D, Ovize M (2008) Increased mitochondrial calcium coexists with decreased reperfusion injury in postconditioned (but not preconditioned) hearts. Am J Physiol Heart Circ Physiol 294:H386–H391PubMedCrossRef

Argaud L, Gateau-Roesch O, Chalabreysse L, Gomez L, Loufouat J, Thivolet-Bejui F, Robert D, Ovize M (2004) Preconditioning delays Ca²⁺-induced mitochondrial permeability transition. Cardiovasc Res 61:115–122PubMedCrossRef

Argaud L, Gateau-Roesch O, Muntean D, Chalabreysse L, Loufouat J, Robert D, Ovize M (2005) Specific inhibition of the mitochondrial permeability transition prevents lethal reperfusion injury. J Mol Cell Cardiol 38:367–374PubMedCrossRef

Argaud L, Gateau-Roesch O, Raisky O, Loufouat J, Robert D, Ovize M (2005) Postconditioning inhibits mitochondrial permeability transition. Circulation 111:194–197PubMedCrossRef

Asimakis GK, Inners-McBride K, Medellin G, Conti VR (1992) Ischemic preconditioning attenuates acidosis and postischemic dysfunction in isolated rat heart. Am J Physiol 263:H887–H894PubMed

10.

Avkiran M, Gross G, Karmazyn M, Klein H, Murphy E, Ytrehus K (2001) Na⁺/H⁺ exchange in ischemia, reperfusion and preconditioning. Cardiovasc Res 50:162–166PubMedCrossRef

11.

Baines CP, Kaiser RA, Purcell NH, Blair NS, Osinska H, Hambleton MA, Brunskill EW, Sayen MR, Gottlieb RA, Dorn GW, Robbins J, Molkentin JD (2005) Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature 434:658–662PubMedCrossRef

12.

Baines CP, Kaiser RA, Sheiko T, Craigen WJ, Molkentin JD (2007) Voltage-dependent anion channels are dispensable for mitochondrial-dependent cell death. Nat Cell Biol 9:550–555PubMedCrossRef

13.

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

14.

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

15.

Bijur GN, Jope RS (2003) Rapid accumulation of Akt in mitochondria following phosphatidylinositol 3-kinase activation. J Neurochem 87:1427–1435PubMedCrossRef

16.

Bopassa JC, Ferrera R, Gateau-Roesch O, Couture-Lepetit E, Ovize M (2006) PI 3-kinase regulates the mitochondrial transition pore in controlled reperfusion and postconditioning. Cardiovasc Res 69:178–185PubMedCrossRef

17.

Burley DS, Ferdinandy P, Baxter GF (2007) Cyclic GMP and protein kinase-G in myocardial ischaemia-reperfusion: opportunities and obstacles for survival signaling. Br J Pharmacol 152:855–869PubMedCrossRef

18.

Clarke SJ, Khaliulin I, Das M, Parker JE, Heesom KJ, Halestrap AP (2008) Inhibition of mitochondrial permeability transition pore opening by ischemic preconditioning is probably mediated by reduction of oxidative stress rather than mitochondrial protein phosphorylation. Circ Res 102:1082–1090PubMedCrossRef

19.

Cohen MV, Yang XM, Downey JM (2007) The pH hypothesis of postconditioning: staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis. Circulation 115:1895–1903PubMedCrossRef

20.

Cohen MV, Yang XM, Downey JM (2008) Acidosis, oxygen, and interference with mitochondrial permeability transition pore formation in the early minutes of reperfusion are critical to postconditioning’s success. Basic Res Cardiol 103:464–471PubMedCrossRef

21.

Costa AD, Garlid KD (2008) Intramitochondrial signaling: interactions among mitoKATP, PKCepsilon, ROS, and MPT. Am J Physiol Heart Circ Physiol 295:H874–H882PubMedCrossRef

22.

Costa AD, Garlid KD, West IC, Lincoln TM, Downey JM, Cohen MV, Critz SD (2005) Protein kinase G transmits the cardioprotective signal from cytosol to mitochondria. Circ Res 97:329–336PubMedCrossRef

23.

Costa AD, Jakob R, Costa CL, Andrukhiv K, West IC, Garlid KD (2006) The mechanism by which the mitochondrial ATP-sensitive K⁺ channel opening and H2O2 inhibit the mitochondrial permeability transition. J Biol Chem 281:20801–20808PubMedCrossRef

24.

Costa AD, Quinlan CL, Andrukhiv A, West IC, Jaburek M, Garlid KD (2006) The direct physiological effects of mitoK(ATP) opening on heart mitochondria. Am J Physiol Heart Circ Physiol 290:H406–H415PubMedCrossRef

25.

Crestanello JA, Doliba NM, Babsky AM, Doliba NM, Niibori K, Osbakken MD, Whitman GJ (2000) Opening of potassium channels protects mitochondrial function from calcium overload. J Surg Res 94:116–123PubMedCrossRef

26.

Crestanello JA, Lingle DM, Kamelgard J, Millili J, Whitman GJ (1996) Ischemic preconditioning decreases oxidative stress during reperfusion: a chemiluminescence study. J Surg Res 65:53–58PubMedCrossRef

27.

Cribbs JT, Strack S (2007) Reversible phosphorylation of Drp1 by cyclic AMP-dependent protein kinase and calcineurin regulates mitochondrial fission and cell death. EMBO Rep 8:939–944PubMedCrossRef

28.

Crompton M, Barksby E, Johnson N, Capano M (2002) Mitochondrial intermembrane junctional complexes and their involvement in cell death. Biochimie 84:143–152PubMedCrossRef

29.

Crompton M, Costi A (1988) Kinetic evidence for a heart mitochondrial pore activated by Ca²⁺, inorganic phosphate and oxidative stress. A potential mechanism for mitochondrial dysfunction during cellular Ca²⁺ overload. Eur J Biochem 178:489–501PubMedCrossRef

30.

Crompton M, Ellinger H, Costi A (1988) Inhibition by cyclosporin A of a Ca²⁺-dependent pore in heart mitochondria activated by inorganic phosphate and oxidative stress. Biochem J 255:357–360PubMed

31.

Darling CE, Jiang R, Maynard M, Whittaker P, Vinten-Johansen J, Przyklenk K (2005) Postconditioning via stuttering reperfusion limits myocardial infarct size in rabbit hearts: role of ERK1/2. Am J Physiol Heart Circ Physiol 289:H1618–H1626PubMedCrossRef

32.

Das S, Wong R, Rajapakse N, Murphy E, Steenbergen C (2008) Glycogen synthase kinase 3 inhibition slows mitochondrial adenine nucleotide transport and regulates voltage-dependent anion channel phosphorylation. Circ Res 103:983–991PubMedCrossRef

33.

Davidson SM, Hausenloy D, Duchen MR, Yellon DM (2006) Signalling via the reperfusion injury signalling kinase (RISK) pathway links closure of the mitochondrial permeability transition pore to cardioprotection. Int J Biochem Cell Biol 38:414–419PubMedCrossRef

34.

Di Lisa F, Bernardi P (2006) Mitochondria and ischemia-reperfusion injury of the heart: fixing a hole. Cardiovasc Res 70:191–199PubMedCrossRef

35.

Dimmer KS, Scorrano L (2006) (De)constructing mitochondria: what for? Physiology (Bethesda) 21:233–241

36.

Downey JM, Davis AM, Cohen MV (2007) Signaling pathways in ischemic preconditioning. Heart Fail Rev 12:181–188PubMedCrossRef

37.

Fang J, Wu L, Chen L (2008) Postconditioning attenuates cardiocyte ultrastructure injury and apoptosis by blocking mitochondrial permeability transition in rats. Acta Cardiol 63:377–387PubMedCrossRef

38.

Forbes RA, Steenbergen C, Murphy E (2001) Diazoxide-induced cardioprotection requires signaling through a redox-sensitive mechanism. Circ Res 88:802–809PubMedCrossRef

39.

Frank S, Gaume B, Bergmann-Leitner ES, Leitner WW, Robert EG, Catez F, Smith CL, Youle RJ (2001) The role of dynamin-related protein 1, a mediator of mitochondrial fission, in apoptosis. Dev Cell 1:515–525PubMedCrossRef

40.

Frezza C, Cipolat S, Martins dB, Micaroni M, Beznoussenko GV, Rudka T, Bartoli D, Polishuck RS, Danial NN, De Strooper B, Scorrano L (2006) OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 126:177–189PubMedCrossRef

41.

Fryer RM, Eells JT, Hsu AK, Henry MM, Gross GJ (2000) Ischemic preconditioning in rats: role of mitochondrial K(ATP) channel in preservation of mitochondrial function. Am J Physiol Heart Circ Physiol 278:H305–H312PubMed

42.

Fujita M, Asanuma H, Hirata A, Wakeno M, Takahama H, Sasaki H, Kim J, Takashima S, Tsukamoto O, Minamino T, Shinozaki Y, Tomoike H, Hori M, Kitakaze M (2007) Prolonged transient acidosis during early reperfusion contributes to the cardioprotective effects of postconditioning. Am J Physiol Heart Circ Physiol 292:H2004–H2008PubMedCrossRef

43.

Garlid KD (2000) Opening mitochondrial K(ATP) in the heart––what happens, and what does not happen. Basic Res Cardiol 95:275–279PubMedCrossRef

44.

Gomez L, Paillard M, Thibault H, Derumeaux G, Ovize M (2008) Inhibition of GSK3beta by postconditioning is required to prevent opening of the mitochondrial permeability transition pore during reperfusion. Circulation 117:2761–2768PubMedCrossRef

45.

Gomez L, Thibault H, Gharib A, Dumont JM, Vuagniaux G, Scalfaro P, Derumeaux G, Ovize M (2007) Inhibition of mitochondrial permeability transition improves functional recovery and reduces mortality following acute myocardial infarction in mice. Am J Physiol Heart Circ Physiol 293:H1654–H1661PubMedCrossRef

46.

Gottlob K, Majewski N, Kennedy S, Kandel E, Robey RB, Hay N (2001) Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase. Genes Dev 15:1406–1418PubMedCrossRef

47.

Griffiths EJ, Halestrap AP (1993) Protection by Cyclosporin A of ischemia/reperfusion-induced damage in isolated rat hearts. J Mol Cell Cardiol 25:1461–1469PubMedCrossRef

48.

Griffiths EJ, Halestrap AP (1995) Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion. Biochem J 307(Pt 1):93–98PubMed

49.

Gross ER, Hsu AK, Gross GJ (2004) Opioid-induced cardioprotection occurs via glycogen synthase kinase beta inhibition during reperfusion in intact rat hearts. Circ Res 94:960–966PubMedCrossRef

50.

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

51.

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

52.

Hausenloy DJ (2009) Signaling pathways in ischemic postconditioning. Thromb Haemost (in press)

53.

Hausenloy DJ, Duchen MR, Yellon DM (2003) Inhibiting mitochondrial permeability transition pore opening at reperfusion protects against ischaemia-reperfusion injury. Cardiovasc Res 60:617–625PubMedCrossRef

54.

Hausenloy DJ, Maddock HL, Baxter GF, Yellon DM (2002) Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning? Cardiovasc Res 55:534–543PubMedCrossRef

55.

Hausenloy DJ, Scorrano L (2007) Targeting cell death. Clin Pharmacol Ther 82:370–373PubMedCrossRef

56.

Hausenloy DJ, Tsang A, Yellon DM (2005) The reperfusion injury salvage kinase pathway: a common target for both ischemic preconditioning and postconditioning. Trends Cardiovasc Med 15:69–75PubMedCrossRef

57.

Hausenloy DJ, Wynne AM, Yellon DM (2007) Ischemic preconditioning targets the reperfusion phase. Basic Res Cardiol 102:445–452PubMedCrossRef

58.

Hausenloy DJ, Yellon DM (2003) The mitochondrial permeability transition pore: its fundamental role in mediating cell death during ischaemia and reperfusion. J Mol Cell Cardiol 35:339–341PubMedCrossRef

59.

Hausenloy DJ, Yellon DM (2004) Adenosine-induced second window of protection is mediated by inhibition of mitochondrial permeability transition pore opening at the time of reperfusion. Cardiovasc Drugs Ther 18:79–80PubMedCrossRef

60.

Hausenloy DJ, Yellon DM (2004) New directions for protecting the heart against ischaemia-reperfusion injury: targeting the reperfusion injury salvage kinase (RISK)-pathway. Cardiovasc Res 61:448–460PubMedCrossRef

61.

Hausenloy DJ, Yellon DM (2007) Preconditioning and postconditioning: united at reperfusion. Pharmacol Ther 116:173–191PubMedCrossRef

62.

Hausenloy DJ, Yellon DM (2007) Reperfusion injury salvage kinase signalling: taking a RISK for cardioprotection. Heart Fail Rev 12:217–234PubMedCrossRef

63.

Hausenloy DJ, Yellon DM, Mani-Babu S, Duchen MR (2004) Preconditioning protects by inhibiting the mitochondrial permeability transition. Am J Physiol Heart Circ Physiol 287:H841–H849PubMedCrossRef

64.

Haworth RA, Hunter DR (1979) The Ca²⁺-induced membrane transition in mitochondria. II. Nature of the Ca²⁺ trigger site. Arch Biochem Biophys 195:460–467PubMedCrossRef

65.

Heusch G (2004) Postconditioning: old wine in a new bottle? J Am Coll Cardiol 44:1111–1112PubMedCrossRef

66.

Hori M, Kitakaze M, Sato H, Takashima S, Iwakura K, Inoue M, Kitabatake A, Kamada T (1991) Staged reperfusion attenuates myocardial stunning in dogs. Role of transient acidosis during early reperfusion. Circulation 84:2135–2145PubMed

67.

Hunter DR, Haworth RA (1979) The Ca²⁺-induced membrane transition in mitochondria. I. The protective mechanisms. Arch Biochem Biophys 195:453–459PubMedCrossRef

68.

Inserte J, Barba I, Hernando V, Abellan A, Ruiz-Meana M, Rodriguez-Sinovas A, Garcia-Dorado D (2008) Effect of acidic reperfusion on prolongation of intracellular acidosis and myocardial salvage. Cardiovasc Res 77:782–790PubMedCrossRef

69.

Inserte J, Barba I, Hernando V, Garcia-Dorado D (2009) Delayed recovery of intracellular acidosis during reperfusion prevents calpain activation and determines protection in postconditioned myocardium. Cardiovasc Res 81:116–122PubMedCrossRef

70.

Jaburek M, Costa AD, Burton JR, Costa CL, Garlid KD (2006) Mitochondrial PKC epsilon and mitochondrial ATP-sensitive K⁺ channel copurify and coreconstitute to form a functioning signaling module in proteoliposomes. Circ Res 99:878–883PubMedCrossRef

71.

Javadov SA, Clarke S, Das M, Griffiths EJ, Lim KH, Halestrap AP (2003) Ischaemic preconditioning inhibits opening of mitochondrial permeability transition pores in the reperfused rat heart. J Physiol 549:513–524

72.

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

73.

Kevin LG, Camara AK, Riess ML, Novalija E, Stowe DF (2003) Ischemic preconditioning alters real-time measure of O₂ radicals in intact hearts with ischemia and reperfusion. Am J Physiol Heart Circ Physiol 284:H566–H574PubMed

74.

Kida M, Fujiwara H, Ishida M, Kawai C, Ohura M, Miura I, Yabuuchi Y (1991) Ischemic preconditioning preserves creatine phosphate and intracellular pH. Circulation 84:2495–2503PubMed

75.

Kim JS, Jin Y, Lemasters JJ (2006) Reactive oxygen species, but not Ca²⁺ overloading, trigger pH- and mitochondrial permeability transition-dependent death of adult rat myocytes after ischemia-reperfusion. Am J Physiol Heart Circ Physiol 290:H2024–H2034PubMedCrossRef

76.

Kim JS, Ohshima S, Pediaditakis P, Lemasters JJ (2004) Nitric oxide: a signaling molecule against mitochondrial permeability transition- and pH-dependent cell death after reperfusion. Free Radic Biol Med 37:1943–1950PubMedCrossRef

77.

Kin H, Zatta AJ, Lofye MT, Amerson BS, Halkos ME, Kerendi F, Zhao ZQ, Guyton RA, Headrick JP, Vinten-Johansen J (2005) Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine. Cardiovasc Res 67:124–133PubMedCrossRef

78.

Kitakaze M, Takashima S, Funaya H, Minamino T, Node K, Shinozaki Y, Mori H, Hori M (1997) Temporary acidosis during reperfusion limits myocardial infarct size in dogs. Am J Physiol 272:H2071–H2078PubMed

79.

Kobara M, Tatsumi T, Matoba S, Yamahara Y, Nakagawa C, Ohta B, Matsumoto T, Inoue D, Asayama J, Nakagawa M (1996) Effect of ischemic preconditioning on mitochondrial oxidative phosphorylation and high energy phosphates in rat hearts. J Mol Cell Cardiol 28:417–428PubMedCrossRef

80.

Kobayashi H, Miura T, Ishida H, Miki T, Tanno M, Yano T, Sato T, Hotta H, Shimamoto K (2008) Limitation of infarct size by erythropoietin is associated with translocation of Akt to the mitochondria after reperfusion. Clin Exp Pharmacol Physiol 35:812–819PubMedCrossRef

81.

Kokoszka JE, Waymire KG, Levy SE, Sligh JE, Cai J, Jones DP, MacGregor GR, Wallace DC (2004) The ADP/ATP translocator is not essential for the mitochondrial permeability transition pore. Nature 427:461–465PubMedCrossRef

82.

Kong D, Xu L, Yu Y, Zhu W, Andrews DW, Yoon Y, Kuo TH (2005) Regulation of Ca²⁺-induced permeability transition by Bcl-2 is antagonized by Drpl and hFis1. Mol Cell Biochem 272:187–199PubMedCrossRef

83.

Korge P, Honda HM, Weiss JN (2002) Protection of cardiac mitochondria by diazoxide and protein kinase C: implications for ischemic preconditioning. Proc Natl Acad Sci USA 99:3312–3317PubMedCrossRef

84.

Laclau MN, Boudina S, Thambo JB, Tariosse L, Gouverneur G, Bonoron-Adele S, Saks VA, Garlid KD, Dos SP (2001) Cardioprotection by ischemic preconditioning preserves mitochondrial function and functional coupling between adenine nucleotide translocase and creatine kinase. J Mol Cell Cardiol 33:947–956PubMedCrossRef

85.

Leung AW, Halestrap AP (2008) Recent progress in elucidating the molecular mechanism of the mitochondrial permeability transition pore. Biochim Biophys Acta 1777:946–952PubMedCrossRef

86.

Lim SY, Davidson SM, Hausenloy DJ, Yellon DM (2007) Preconditioning and postconditioning: the essential role of the mitochondrial permeability transition pore. Cardiovasc Res 75:530–535PubMedCrossRef

87.

Majewski N, Nogueira V, Bhaskar P, Coy PE, Skeen JE, Gottlob K, Chandel NS, Thompson CB, Robey RB, Hay N (2004) Hexokinase-mitochondria interaction mediated by Akt is required to inhibit apoptosis in the presence or absence of Bax and Bak. Mol Cell 16:819–830PubMedCrossRef

88.

Miyamoto S, Howes AL, Adams JW, Dorn GW, Brown JH (2005) Ca²⁺ dysregulation induces mitochondrial depolarization and apoptosis: role of Na⁺/Ca²⁺ exchanger and AKT. J Biol Chem 280:38505–38512PubMedCrossRef

89.

Miyamoto S, Murphy AN, Brown JH (2008) Akt mediates mitochondrial protection in cardiomyocytes through phosphorylation of mitochondrial hexokinase-II. Cell Death Differ 15:521–529PubMedCrossRef

90.

Murata M, Akao M, O’Rourke B, Marban E (2001) Mitochondrial ATP-sensitive potassium channels attenuate matrix Ca(2+) overload during simulated ischemia and reperfusion: possible mechanism of cardioprotection. Circ Res 89:891–898PubMedCrossRef

91.

Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136PubMed

92.

Murry CE, Richard VJ, Reimer KA, Jennings RB (1990) Ischemic preconditioning slows energy metabolism and delays ultrastructural damage during a sustained ischemic episode. Circ Res 66:913–931PubMed

93.

Mykytenko J, Reeves JG, Kin H, Wang NP, Zatta AJ, Jiang R, Guyton RA, Vinten-Johansen J, Zhao ZQ (2008) Persistent beneficial effect of postconditioning against infarct size: role of mitochondrial K(ATP) channels during reperfusion. Basic Res Cardiol 103:472–484PubMedCrossRef

94.

Nakagawa T, Shimizu S, Watanabe T, Yamaguchi O, Otsu K, Yamagata H, Inohara H, Kubo T, Tsujimoto Y (2005) Cyclophilin D-dependent mitochondrial permeability transition regulates some necrotic but not apoptotic cell death. Nature 434:652–658PubMedCrossRef

95.

Narayan P, Mentzer RM Jr, Lasley RD (2001) Adenosine A1 receptor activation reduces reactive oxygen species and attenuates stunning in ventricular myocytes. J Mol Cell Cardiol 33:121–129PubMedCrossRef

96.

Nazareth W, Yafei N, Crompton M (1991) Inhibition of anoxia-induced injury in heart myocytes by cyclosporin A. J Mol Cell Cardiol 23:1351–1354PubMedCrossRef

97.

Neuspiel M, Zunino R, Gangaraju S, Rippstein P, McBride H (2005) Activated mitofusin 2 signals mitochondrial fusion, interferes with Bax activation, and reduces susceptibility to radical induced depolarization. J Biol Chem 280:25060–25070PubMedCrossRef

98.

Nishihara M, Miura T, Miki T, Tanno M, Yano T, Naitoh K, Ohori K, Hotta H, Terashima Y, Shimamoto K (2007) Modulation of the mitochondrial permeability transition pore complex in GSK-3beta-mediated myocardial protection. J Mol Cell Cardiol 43:564–570PubMedCrossRef

99.

Nishino Y, Webb IG, Davidson SM, Ahmed AI, Clark JE, Jacquet S, Shah AM, Miura T, Yellon DM, Avkiran M, Marber MS (2008) Glycogen synthase kinase-3 inactivation is not required for ischemic preconditioning or postconditioning in the mouse. Circ Res 103:307–314PubMedCrossRef

100.

Ozcan C, Bienengraeber M, Dzeja PP, Terzic A (2002) Potassium channel openers protect cardiac mitochondria by attenuating oxidant stress at reoxygenation. Am J Physiol Heart Circ Physiol 282:H531–H539PubMed

101.

Penna C, Mancardi D, Rastaldo R, Losano G, Pagliaro P (2007) Intermittent activation of bradykinin B2 receptors and mitochondrial KATP channels trigger cardiac postconditioning through redox signaling. Cardiovasc Res 75:168–177PubMedCrossRef

102.

Penna C, Rastaldo R, Mancardi D, Raimondo S, Cappello S, Gattullo D, Losano G, Pagliaro P (2006) Post-conditioning induced cardioprotection requires signaling through a redox-sensitive mechanism, mitochondrial ATP-sensitive K⁺ channel and protein kinase C activation. Basic Res Cardiol 101:180–189PubMedCrossRef

103.

Piot C, Croisille P, Staat P, Thibault H, Rioufol G, Mewton N, Elbelghiti R, Cung TT, Bonnefoy E, Angoulvant D, Macia C, Raczka F, Sportouch C, Gahide G, Finet G, Andre-Fouet X, Revel D, Kirkorian G, Monassier JP, Derumeaux G, Ovize M (2008) Effect of cyclosporine on reperfusion injury in acute myocardial infarction. N Engl J Med 359:473–481PubMedCrossRef

104.

Piriou V, Chiari P, Gateau-Roesch O, Argaud L, Muntean D, Salles D, Loufouat J, Gueugniaud PY, Lehot JJ, Ovize M (2004) Desflurane-induced preconditioning alters calcium-induced mitochondrial permeability transition. Anesthesiology 100:581–588PubMedCrossRef

105.

Quinlan CL, Costa AD, Costa CL, Pierre SV, Dos SP, Garlid KD (2008) Conditioning the heart induces formation of signalosomes that interact with mitochondria to open mitoKATP channels. Am J Physiol Heart Circ Physiol 295:H953–H961PubMedCrossRef

106.

Rajesh KG, Sasaguri S, Zhitian Z, Suzuki R, Asakai R, Maeda H (2003) Second window of ischemic preconditioning regulates mitochondrial permeability transition pore by enhancing Bcl-2 expression. Cardiovasc Res 59:297–307PubMedCrossRef

107.

Raphael J, Drenger B, Rivo J, Berenshtein E, Chevion M, Gozal Y (2005) Ischemic preconditioning decreases the reperfusion-related formation of hydroxyl radicals in a rabbit model of regional myocardial ischemia and reperfusion: the role of K(ATP) channels. Free Radic Res 39:747–754PubMedCrossRef

108.

Rehring TF, Shapiro JI, Cain BS, Meldrum DR, Cleveland JC, Harken AH, Banerjee A (1998) Mechanisms of pH preservation during global ischemia in preconditioned rat heart: roles for PKC and NHE. Am J Physiol 275:H805–H813PubMed

109.

Robin E, Guzy RD, Loor G, Iwase H, Waypa GB, Marks JD, Hoek TL, Schumacker PT (2007) Oxidant stress during simulated ischemia primes cardiomyocytes for cell death during reperfusion. J Biol Chem 282:19133–19143PubMedCrossRef

110.

Ruiz-Meana M, Garcia-Dorado D, Miro-Casas E, Abellan A, Soler-Soler J (2006) Mitochondrial Ca(2+) uptake during simulated ischemia does not affect permeability transition pore opening upon simulated reperfusion. Cardiovasc Res 71:715–724PubMedCrossRef

111.

Snabaitis AK, Cuello F, Avkiran M (2008) Protein kinase B/Akt phosphorylates and inhibits the cardiac Na⁺/H⁺ exchanger NHE1. Circ Res 103:881–890PubMedCrossRef

112.

Steenbergen C, Perlman ME, London RE, Murphy E (1993) Mechanism of preconditioning. Ionic alterations. Circ Res 72:112–125PubMed

113.

Sun HY, Wang NP, Kerendi F, Halkos M, Kin H, Guyton RA, Vinten-Johansen J, Zhao ZQ (2005) Hypoxic postconditioning reduces cardiomyocyte loss by inhibiting ROS generation and intracellular Ca²⁺ overload. Am J Physiol Heart Circ Physiol 288:H1900–H1908PubMedCrossRef

114.

Thibault H, Piot C, Staat P, Bontemps L, Sportouch C, Rioufol G, Cung TT, Bonnefoy E, Angoulvant D, Aupetit JF, Finet G, Andre-Fouet X, Macia JC, Raczka F, Rossi R, Itti R, Kirkorian G, Derumeaux G, Ovize M (2008) Long-term benefit of postconditioning. Circulation 117:1037–1044PubMedCrossRef

115.

Tong H, Imahashi K, Steenbergen C, Murphy E (2002) Phosphorylation of glycogen synthase kinase-3beta during preconditioning through a phosphatidylinositol-3-kinase-dependent pathway is cardioprotective. Circ Res 90:377–379PubMedCrossRef

116.

Tosaki A, Cordis GA, Szerdahelyi P, Engelman RM, Das DK (1994) Effects of preconditioning on reperfusion arrhythmias, myocardial functions, formation of free radicals, and ion shifts in isolated ischemic/reperfused rat hearts. J Cardiovasc Pharmacol 23:365–373PubMedCrossRef

117.

Tsang A, Hausenloy DJ, Mocanu MM, Yellon DM (2004) Postconditioning: a form of “modified reperfusion” protects the myocardium by activating the phosphatidylinositol 3-kinase-Akt pathway. Circ Res 95:230–232PubMedCrossRef

118.

Tsang A, Hausenloy DJ, Yellon DM (2005) Myocardial postconditioning: reperfusion injury revisited. Am J Physiol Heart Circ Physiol 289:H2–H7PubMedCrossRef

119.

Vanden Hoek T, Becker LB, Shao ZH, Li CQ, Schumacker PT (2000) Preconditioning in cardiomyocytes protects by attenuating oxidant stress at reperfusion. Circ Res 86:541–548

120.

Vanden Hoek TL, Becker LB, Shao Z, Li C, Schumacker PT (1998) Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes. J Biol Chem 273:18092–18098CrossRef

121.

Vinten-Johansen J (2007) Postconditioning: a mechanical maneuver that triggers biological and molecular cardioprotective responses to reperfusion. Heart Fail Rev 12:235–244PubMedCrossRef

122.

Wang L, Cherednichenko G, Hernandez L, Halow J, Camacho SA, Figueredo V, Schaefer S (2001) Preconditioning limits mitochondrial Ca(2+) during ischemia in rat hearts: role of K(ATP) channels. Am J Physiol Heart Circ Physiol 280:H2321–H2328PubMed

123.

Weiss JN, Korge P, Honda HM, Ping P (2003) Role of the mitochondrial permeability transition in myocardial disease. Circ Res 93:292–301PubMedCrossRef

124.

Wolfe CL, Sievers RE, Visseren FL, Donnelly TJ (1993) Loss of myocardial protection after preconditioning correlates with the time course of glycogen recovery within the preconditioned segment. Circulation 87:881–892PubMed

125.

Xiao XH, Allen DG (1999) Role of Na(+)/H(+) exchanger during ischemia and preconditioning in the isolated rat heart. Circ Res 85:723–730PubMed

126.

Xiao XH, Allen DG (2000) Activity of the Na(+)/H(+) exchanger is critical to reperfusion damage and preconditioning in the isolated rat heart. Cardiovasc Res 48:244–253PubMedCrossRef

127.

Xu M, Wang Y, Hirai K, Ayub A, Ashraf M (2001) Calcium preconditioning inhibits mitochondrial permeability transition and apoptosis. Am J Physiol Heart Circ Physiol 280:H899–H908PubMed

128.

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

129.

Yabe K, Nasa Y, Sato M, Iijima R, Takeo S (1997) Preconditioning preserves mitochondrial function and glycolytic flux during an early period of reperfusion in perfused rat hearts. Cardiovasc Res 33:677–685PubMedCrossRef

130.

Yang XM, Proctor JB, Cui L, Krieg T, Downey JM, Cohen MV (2004) Multiple, brief coronary occlusions during early reperfusion protect rabbit hearts by targeting cell signaling pathways. J Am Coll Cardiol 44:1103–1110PubMedCrossRef

131.

Yellon DM, Downey JM (2003) Preconditioning the myocardium: from cellular physiology to clinical cardiology. Physiol Rev 83:1113–1151PubMed

132.

Yellon DM, Hausenloy DJ (2007) Myocardial reperfusion injury. N Engl J Med 357:1121–1135PubMedCrossRef

133.

Ylitalo KV, Ala-Rami A, Liimatta EV, Peuhkurinen KJ, Hassinen IE (2000) Intracellular free calcium and mitochondrial membrane potential in ischemia/reperfusion and preconditioning. J Mol Cell Cardiol 32:1223–1238PubMedCrossRef

134.

Yoon Y, Krueger EW, Oswald BJ, McNiven MA (2003) The mitochondrial protein hFis1 regulates mitochondrial fission in mammalian cells through an interaction with the dynamin-like protein DLP1. Mol Cell Biol 23:5409–5420PubMedCrossRef

135.

Yu T, Sheu SS, Robotham JL, Yoon Y (2008) Mitochondrial fission mediates high glucose-induced cell death through elevated production of reactive oxygen species. Cardiovasc Res 79:341–351PubMedCrossRef

136.

Zatta AJ, Kin H, Lee G, Wang N, Jiang R, Lust R, Reeves JG, Mykytenko J, Guyton RA, Zhao ZQ, Vinten-Johansen J (2006) Infarct-sparing effect of myocardial postconditioning is dependent on protein kinase C signalling. Cardiovasc Res 70:315–324PubMedCrossRef

137.

Zatta AJ, Kin H, Yoshishige D, Jiang R, Wang N, Reeves JG, Mykytenko J, Guyton RA, Zhao ZQ, Caffrey JL, Vinten-Johansen J (2008) Evidence that cardioprotection by postconditioning involves preservation of myocardial opioid content and selective opioid receptor activation. Am J Physiol Heart Circ Physiol 294:H1444–H1451PubMedCrossRef

138.

Zhao ZQ, Corvera JS, Halkos ME, Kerendi F, Wang NP, Guyton RA, Vinten-Johansen J (2003) Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning. Am J Physiol Heart Circ Physiol 285:H579–H588PubMed

139.

Zuurbier CJ, Eerbeek O, Meijer AJ (2005) Ischemic preconditioning, insulin, and morphine all cause hexokinase redistribution. Am J Physiol Heart Circ Physiol 289:H496–H499PubMedCrossRef

Title: The mitochondrial permeability transition pore as a target for preconditioning and postconditioning
Authors: Derek J. Hausenloy
Sang-Bing Ong
Derek M. Yellon
Publication date: 01-03-2009
Publisher: D. Steinkopff-Verlag
Published in: Basic Research in Cardiology / Issue 2/2009
Print ISSN: 0300-8428
Electronic ISSN: 1435-1803
DOI: https://doi.org/10.1007/s00395-009-0010-x

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