Molecular mechanisms of apoptosis in the cardiac myocyte

Current Opinion in Pharmacology

Volumn 1, Issue 2, 2001, Pages 141-150

  Bishopric, Nanette H ^a   Andreka, Peter ^a   Slepak, Tatiana ^a   Webster, Keith A ^b  

^a UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^b NONE

Author keywords

Bcl 2 related proteins; Beta adrenergic signalling; Calcineurin; Cytokines; Drug Discovery; Hypertrophy; Hypoxia; MAP kinases; Mitochondria; Molecular Medicine; Nitric oxide; Pharmacology; Redox stress

Indexed keywords

CYTOCHROME C; FAS ANTIGEN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASES; NITRIC OXIDE; ONCOPROTEIN; PROTO ONCOGENE PROTEINS C BCL 2; TUMOR NECROSIS FACTOR RECEPTOR;

ANIMAL; APOPTOSIS; CELL HYPOXIA; CYTOLOGY; HEART MITOCHONDRION; HEART MUSCLE; HUMAN; METABOLISM; OXIDATIVE STRESS; PHYSIOLOGY; REVIEW; SIGNAL TRANSDUCTION;

ANIMAL; ANTIGENS, CD95; APOPTOSIS; CELL HYPOXIA; CYTOCHROME C; HUMAN; MITOCHONDRIA, HEART; MITOGEN-ACTIVATED PROTEIN KINASES; MYOCARDIUM; NITRIC OXIDE; OXIDATIVE STRESS; PROTO-ONCOGENE PROTEINS C-BCL-2; RECEPTORS, TUMOR NECROSIS FACTOR; SIGNAL TRANSDUCTION; SUPPORT, NON-U.S. GOV'T; SUPPORT, U.S. GOV'T, P.H.S.;

EID: 0035321910     PISSN: 14714892     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1471-4892(01)00032-7     Document Type: Review

References (93)

1. Wyllie A.H., Kerr J.F.R., Currie A.R. Cell death: significance of apoptosis. Int Rev Cytol. 68:1980;251-306.
2. Sabbah H.N., Sharov V.G. Apoptosis in heart failure. Prog Cardiovasc Dis. 40:1998;549-562.
3. Freude B., Masters T.N., Robicsek F., Fokin A., Kostin S., Zimmermann R., Ullmann C., Lorenz-Meyer S., Schaper J. Apoptosis is initiated by myocardial ischemia and executed during reperfusion. J Mol Cell Cardiol. 32:2000;197-208.
4. Guerra S., Leri A., Wang X., Finato N., Di Loreto C., Beltrami C.A., Kajstura J., Anversa P. Myocyte death in the failing human heart is gender dependent. Circ Res. 85:1999;856-866.
5. Sam F., Sawyer D.B., Chang D.L., Eberli F.R., Ngoy S., Jain M., Amin J., Apstein C.S., Colucci W.S. Progressive left ventricular remodeling and apoptosis late after myocardial infarction in mouse heart. Am J Physiol - Heart Circ Physiol. 279:2000;H422-H428.
6. Zhou Y.T., Grayburn P., Karim A., Shimabukuro M., Higa M., Baetens D., Orci L., Unger R.H. Lipotoxic heart disease in obese rats: implications for human obesity. Proc Natl Acad Sci USA. 97:2000;1784-1789. This paper outlines the potential role of apoptosis induced by NO species and by ceramide in diabetic cardiomyopathy.
7. Tea B.S., Dam T.V., Moreau P., Hamet P., deBlois D. Apoptosis during regression of cardiac hypertrophy in spontaneously hypertensive rats. Temporal regulation and spatial heterogeneity. Hypertension. 34:1999;229-235.
8. Hirota H., Chen J., Betz U.A., Rajewsky K., Gu Y., Ross J. Jr, Muller W., Chien K.R. Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress. Cell. 97:1999;189-198. This paper establishes that endogenous anti-apoptotic signals in the myocyte protect against the development of heart failure in response to acute pressure overload.
9. Zhang D., Gaussin V., Taffet G.E., Belaguli N.S., Yamada M., Schwartz R.J., Michael L.H., Overbeek P.A., Schneider M.D. TAK1 is activated in the myocardium after pressure overload and is sufficient to provoke heart failure in transgenic mice. Nat Med. 6:2000;556-563. TAK1 is an upstream activator of both JNK and p38, both of which have been implicated in apoptotic signaling. These authors show that both apoptosis and heart failure can be induced in transgenic mice by an activated form of TAK1, providing a functional link between the two processes.
10. Francis G.S., Anwar F., Bank A.J., Kubo S.H., Jessurun J. Apoptosis, Bcl-2, and proliferating cell nuclear antigen in the failing human heart: observations made after implantation of left ventricular assist device. J Card Fail. 5:1999;308-315.
11. Petrovic D., Zorc-Pleskovic R., Zorc M. Apoptosis and proliferation of cardiomyocytes in heart failure of different etiologies. Cardiovasc Pathol. 9:2000;149-152.
12. Hengartner M.O. The biochemistry of apoptosis. Nature. 407:2000;770-776.
13. Wollert K.C., Heineke J., Westermann J., Ludde M., Fiedler B., Zierhut W., Laurent D., Bauer M.K., Schulze-Osthoff K., Drexler H. The cardiac Fas (APO-1/CD95) Receptor/Fas ligand system:relation to diastolic wall stress in volume-overload hypertrophy in vivo and activation of the transcription factor AP-1 in cardiac myocytes. Circulation. 101:2000;1172-1178.
14. Filippatos G., Leche C., Sunga R., Tsoukas A., Anthopoulos P., Joshi I., Bifero A., Pick R., Uhal B.D. Expression of FAS adjacent to fibrotic foci in the failing human heart is not associated with increased apoptosis. Am J Physiol. 277:1999;H445-H451.
15. Nelson D.P., Setser E., Hall D.G., Schwartz S.M., Hewitt T., Klevitsky R., Osinska H., Bellgrau D., Duke R.C., Robbins J. Proinflammatory consequences of transgenic fas ligand expression in the heart. J Clin Invest. 105:2000;1199-1208.
16. Nakamura T., Ueda Y., Juan Y., Katsuda S., Takahashi H., Koh E. Fas-mediated apoptosis in adriamycin-induced cardiomyopathy in rats: in vivo study. Circulation. 102:2000;572-578.
17. Li X., Moody M.R., Engel D., Walker S., Clubb F.J. Jr, Sivasubramanian N., Mann D.L., Reid M.B. Cardiac-specific overexpression of tumor necrosis factor-alpha causes oxidative stress and contractile dysfunction in mouse diaphragm. Circulation. 102:2000;1690-1696.
18. Song W., Lu X., Feng Q. Tumor necrosis factor-alpha induces apoptosis via inducible nitric oxide synthase in neonatal mouse cardiomyocytes. Cardiovasc Res. 45:2000;595-602.
19. Kurrelmeyer K.M., Michael L.H., Baumgarten G., Taffet G.E., Peschon J.J., Sivasubramanian N., Entman M.L., Mann D.L. Endogenous tumor necrosis factor protects the adult cardiac myocyte against ischemic-induced apoptosis in a murine model of acute myocardial infarction. Proc Natl Acad Sci USA. 97:2000;5456-5461. The lack of both TNFR-1 and TNFR-2 receptors enhanced, not reduced, the frequency and extent of apoptosis following acute myocardial infarction in mice. This constitutes strong evidence that TNF signaling is not pro-apoptotic in the intact myocardium.
20. Mustapha S., Kirshner A., De Moissac D., Kirshenbaum L.A. A direct requirement of nuclear factor-kappa B for suppression of apoptosis in ventricular myocytes. Am J Physiol - Heart Circ Physiol. 279:2000;H939-H945.
21. Ekhterae D., Lin Z., Lundberg M.S., Crow M.T., Brosius F.C. I.I.I., Nunez G. ARC inhibits cytochrome c release from mitochondria and protects against hypoxia-induced apoptosis in heart-derived H9c2 cells, Circ Res. ee77. 85:1999;70.
22. Cook S.A., Sugden P.H., Clerk A. Regulation of bcl-2 family proteins during development and in response to oxidative stress in cardiac myocytes: association with changes in mitochondrial membrane potential. Circ Res. 85:1999;940-949. An elegant demonstration of the role of Bcl-2-related protein translocation to the mitochondria in cardiac myocyte apoptosis.
23. Stefanelli C., Stanic I., Zini M., Bonavita F., Flamigni F., Zambonin L., Landi L., Pignatti C., Guarnieri C., Caldarera C.M. Polyamines directly induce release of cytochrome c from heart mitochondria. Biochem J. 347:2000;875-880.
24. Bialik S., Cryns V.L., Drincic A., Miyata S., Wollowick A.L., Srinivasan A., Kitsis R.N. The mitochondrial apoptotic pathway is activated by serum and glucose deprivation in cardiac myocytes. Circ Res. 85:1999;403-414.
25. q signalling is mediated by permeability transition pore formation and activation of the mitochondrial death pathway. Circ Res. 87:2000;1180-1187.
26. de Moissac D., Gurevich R.M., Zheng H., Singal P.K., Kirshenbaum L.A. Caspase activation and mitochondrial cytochrome C release during hypoxia-mediated apoptosis of adult ventricular myocytes. J Mol Cell Cardiol. 32:2000;53-63.
27. Burgess D.H., Svensson M., Dandrea T., Gronlund K., Hammarquist F., Orrenius S., Cotgreave I.A. Human skeletal muscle cytosols are refractory to cytochrome c-dependent activation of type-II caspases and lack APAF-1. Cell Death Differ. 6:1999;256-261.
28. Andrieu-Abadie N., Jaffrezou J.P., Hatem S., Laurent G., Levade T., Mercaider J.J. L-carnitine prevents doxorubicin-induced apoptosis of cardiac myocytes: role of inhibition of ceramide generation. FASEB J. 13:1999;1501-1510.
29. Ing D.J., Zang J., Dzau V.J., Webster K.A., Bishopric N.H. Modulation of cytokine-induced cardiac myocyte apoptosis by nitric oxide, Bak and Bcl-x. Circ Res. 84:1999;21-33.
30. Leri A., Fiordaliso F., Setoguchi M., Limana F., Bishopric N.H., Kajstura J., Webster K., Anversa P. Inhibition of p53 function prevents renin-angiotensin system activation and stretch-mediated myocyte apoptosis. Am J Pathol. 157:2000;843-857.
31. McDonald T.E., Grinman M.N., Carthy C.M., Walley K.R. Endotoxin infusion in rats induces apoptotic and survival pathways in hearts. Am J Physiol - Heart Circ Physiol. 279:2000;H2053-H2061.
32. Hu Y., Zou Y., Hala M., Dietrich H., Wick G., Xu Q. Prolonged survival of heart allografts from p53-deficient mice. Transplantation. 69:2000;2634-2640.
33. Latif N., Khan M.A., Birks E., O'Farrell A., Westbrook J., Dunn M.J., Yacoub M.H. Upregulation of the Bcl-2 family of proteins in end stage heart failure. J Am Coll Cardiol. 35:2000;1769-1777.
34. Bartling B., Milting H., Schumann H., Darmer D., Arusoglu L., Koerner M.M., El-Banayosy A., Koerfer R., Holtz J., Zerkowski H.R. Myocardial gene expression of regulators of myocyte apoptosis and myocyte calcium homeostasis during hemodynamic unloading by ventricular assist devices in patients with end-stage heart failure, Circulation. II223. 100:1999;I216-I.
35. Azhar G., Liu L., Zhang X., Wei J.Y. Influence of age on hypoxia/ reoxygenation-induced DNA fragmentation and bcl-2, bcl-xl, bax and fas in the rat heart and brain. Mech Ageing Dev. 112:1999;5-25.
36. Brocheriou V., Hagege A.A., Oubenaissa A., Lambert M., Mallet V.O., Duriez M., Wassef M., Kahn A., Menasche P., Gilgenkrantz H. Cardiac functional improvement by a human Bcl-2 transgene in a mouse model of ischemia/reperfusion injury. J Gene Med. 2:2000;326-333.
37. Xia Z., Dickens M., Raingeaud J., Davis R.J., Greenberg M.E. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science. 270:1995;1326-1331.
38. Laderoute K.R., Webster K.A. Hypoxia/reoxygenation stimulates Jun kinase activity through redox signaling in cardiac myocytes. Circ Res. 80:1997;336-344.
39. Ma X.L., Kumar S., Gao F., Louden C.S., Lopez B.L., Christopher T.A., Wang C., Lee J.C., Feuerstein G.Z., Yue T.L. Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation. 99:1999;1685-1691.
40. Cook S.A., Sugden P.H., Clerk A. Activation of c-Jun N-terminal kinases and p38-mitogen-activated protein kinases in human heart failure secondary to ischaemic heart disease. J Mol Cell Cardiol. 31:1999;1429-1434.
41. Gillespie-Brown J., Fuller S.J., Bogoyevitch M.A., Cowley S., Sugden P.H. The mitogen-activated protein kinase kinase MEK1 stimulates a pattern of gene expression typical of the hypertrophic phenotype in rat ventricular cardiomyocytes. J Biol Chem. 270:1995;28092-28096.
42. 2-terminal kinase in ventricular muscle cells. J Biol Chem. 273:1998;5423-5426.
43. Yue T.L., Wang C., Gu J.L., Ma X.L., Kumar S., Lee J.C., Feuerstein G.Z., Thomas H., Maleeff B., Ohlstein E.H. Inhibition of extracellular signal-regulated kinase enhances ischemia/reoxygenation-induced apoptosis in cultured cardiac myocytes and exaggerates reperfusion injury in isolated perfused heart. Circ Res. 86:2000;692-699.
44. Zhu W., Zou Y., Aikawa R., Harada K., Kudoh S., Uozumi H., Hayashi D., Gu Y., Yamazaki T., Nagai R., et al. MAPK superfamily plays an important role in daunomycin-induced apoptosis of cardiac myocytes. Circulation. 100:1999;2100-2107.
45. Communal C., Colucci W.S., Singh K. p38 mitogen-activated protein kinase pathway protects adult rat ventricular myocytes against beta-adrenergic receptor-stimulated apoptosis. Evidence for Gi-dependent activation. J Biol Chem. 275:2000;19395-19400.
46. Chesley A., Lundberg M.S., Asai T., Xiao R.P., Ohtani S., Lakatta E.G., Crow M.T. The beta2-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through Gi-dependent coupling to phosphatidylinositol 3′-kinase. Circ Res. 87:2000;1172-1179.
47. Mackay K., Mochly-Rosen D. Involvement of a p38 mitogen-activated protein kinase phosphatase in protecting neonatal rat cardiac myocytes from ischemia. J Mol Cell Cardiol. 32:2000;1585-1588.
48. Kang Y.J., Zhou Z.X., Wang G.W., Buridi A., Klein J.B. Suppression by metallothionein of doxorubicin-induced cardiomyocyte apoptosis through inhibition of p38 mitogen-activated protein kinases. J Biol Chem. 275:2000;13690-13698.
49. Craig R., Larkin A., Mingo A.M., Thuerauf D.J., Andrews C., McDonough P.M., Glembotski C.C. p38 MAPK and NF-kappa B collaborate to induce interleukin-6 gene expression and release. Evidence for a cytoprotective autocrine signaling pathway in a cardiac myocyte model system. J Biol Chem. 275:2000;23814-23824. This paper provides a mechanistic explanation for the cytoprotective effects of p38, by showing an interaction with components of the NFκB signaling pathway in cardiac myocytes.
50. Hoover H.E., Thuerauf D.J., Martindale J.J., Glembotski C.C. alpha B-crystallin gene induction and phosphorylation by MKK6-activated p38. A potential role for alpha B-crystallin as a target of the p38 branch of the cardiac stress response. J Biol Chem. 275:2000;23825-23833.
51. Seko Y., Takahashi N., Tobe K., Kadowaki T., Yazaki Y. Pulsatile stretch activates mitogen-activated protein kinase (MAPK) family members and focal adhesion kinase (p125(FAK)) in cultured rat cardiac myocytes. Biochem Biophys Res Commun. 259:1999;8-14.
52. LaPointe M.C., Isenovic E. Interleukin-1beta regulation of inducible nitric oxide synthase and cyclooxygenase-2 involves the p42/44 and p38 MAPK signaling pathways in cardiac myocytes. Hypertension. 33:1999;276-282.
53. Davis R.J. Signal transduction by the JNK group of MAP kinases. Cell. 103:2000;239-252.
54. Minamino T., Yujiri T., Papst P.J., Chan E.D., Johnson G.L., Terada N. MEKK1 suppresses oxidative stress-induced apoptosis of embryonic stem cell-derived cardiac myocytes. Proc Natl Acad Sci USA. 96:1999;15127-15132. An interesting demonstration of a possible cytoprotective role for Jun kinase by inhibition of TNF-α signaling.
55. Andreka P., Dougherty C., Slepak T.I., Webster K.A., Bishopric N.H. Cytoprotection by Jun kinase during nitric oxide-induced cardiac myocyte apoptosis. Circ Res. 88:2001;305-312.
56. q signaling: a common pathway mediates cardiac hypertrophy and apoptotic heart failure. Proc Natl Acad Sci USA. 95:1998;10140-10145.
57. Fiordaliso F., Li B., Latini R., Sonnenblick E.H., Anversa P., Leri A., Kajstura J. Myocyte death in streptozotocin-induced diabetes in rats is angiotensin II-dependent. Lab Invest. 80:2000;513-527.
58. De Windt L.J., Lim H.W., Taigen T., Wencker D., Condorelli G., Dorn G.W. I.I., Kitsis R.N., Molkentin J.D. Calcineurin-mediated hypertrophy protects cardiomyocytes from apoptosis in vitro and in vivo: an apoptosis-independent model of dilated heart failure. Circ Res. 86:2000;255-263.
59. Araki M., Hasegawa K., Iwai-Kanai E., Fujita M., Sawamura T., Kakita T., Wada H., Morimoto T., Sasayama S. Endothelin-1 as a protective factor against beta-adrenergic agonist-induced apoptosis in cardiac myocytes. J Am Coll Cardiol. 36:2000;1411-1418.
60. Iwai-Kanai E., Hasegawa K., Araki M., Kakita T., Morimoto T., Sasayama S. Alpha- and beta-adrenergic pathways differentially regulate cell type-specific apoptosis in rat cardiac myocytes. Circulation. 100:1999;305-311.
61. Sugden P.H. Signaling in myocardial hypertrophy: life after calcineurin? Circ Res. 84:1999;633-646.
62. Bueno O.F., De Windt L.J., Tymitz K.M., Witt S.A., Kimball T.R., Klevitsky R., Hewett T.E., Jones S.P., Lefer D.J., Peng C.F., et al. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J. 19:2000;6341-6350.
63. Saito S., Hiroi Y., Zou Y., Aikawa R., Haruhiro T., Sibasaki F., Yazaki Y., Nagai R., Komuro I. Beta-adrenergic pathway induces apoptosis through calcineurin activation in cardiac myocytes. J Biol Chem. 275:2000;34528-34533.
64. Reiss K., Cheng W., Pierzchalski P., Kodali S., Li B., Wang S., Liu Y., Anversa P. Insulin-like growth factor-1 receptor and its ligand regulate the reentry of adult ventricular myocytes into the cell cycle. Exp Cell Res. 235:1997;198-209.
65. 3 kinse/Akt pathway in several models of myocyte injury. See also [69,70].
66. Li Q., Li B., Wang X., Leri A., Jana K.P., Liu Y., Kajstura J., Baserga R., Anversa P. Overexpression of insulin-like growth factor-1 in mice protects from myocyte death after infarction, attenuating ventricular dilation, wall stress, and cardiac hypertrophy. J Clin Invest. 100:1997;1991-1999.
67. Kuwahara K., Saito Y., Kishimoto I., Miyamoto Y., Harada M., Ogawa E., Hamanaka I., Kajiyama N., Takahashi N., Izumi T., et al. Cardiotrophin-1 phosphorylates akt and BAD, and prolongs cell survival via a PI3K-dependent pathway in cardiac myocytes. J Mol Cell Cardiol. 32:2000;1385-1394.
68. Shioi T., Kang P.M., Douglas P.S., Hampe J., Yballe C.M., Lawitts J., Cantley L.C., Izumo S. The conserved phosphoinositide 3-kinase pathway determines heart size in mice. EMBO J. 19:2000;2537-2548.
69. Matsui T., Li L., del Monte F., Fukui Y., Franke T.F., Hajjar R.J., Rosenzweig A. Adenoviral gene transfer of activated phosphatidylinositol 3′-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro. Circulation. 100:1999;2373-2379.
70. Wu W., Lee W.L., Wu Y.Y., Chen D., Liu T.J., Jang A., Sharma P.M., Wang P.H. Expression of constitutively active phosphatidylinositol 3 kinase inhibits activation of caspase 3 and apoptosis of cardiac muscle cells. J Biol Chem. 275:2000;40113-40119.
71. Li B., Setoguchi M., Wang X., Andreoli A.M., Leri A., Malhotra A., Kajstura J., Anversa P. Insulin-like growth factor-1 attenuates the detrimental impact of nonocclusive coronary artery constriction on the heart. Circ Res. 84:1999;1007-1019.
72. Zaugg M., Xu W., Lucchinetti E., Shafiq S.A., Jamali N.Z., Siddiqui M.A. Beta-adrenergic receptor subtypes differentially affect apoptosis in adult rat ventricular myocytes. Circulation. 102:2000;344-350.
73. 1-adrenergic receptor in transgenic mice. J Mol Cell Cardiol. 32:2000;817-830.
74. Communal C., Singh K., Sawyer D.B., Colucci W.S. Opposing effects of beta1-and beta2-adrenergic receptors on cardiac myocyte apoptosis: role of a pertussis toxin-sensitive G protein. Circulation. 100:1999;2210-2212.
75. Wu C.-F., Bishopric N.H., Pratt R.E. Atrial natriuretic peptide induces apoptosis in rat cardiac myocytes. J Biol Chem. 272:1997;14860-14866.
76. 3 adenosine receptor activation and its suppression by isoproterenol. Exp Cell Res. 257:2000;111-126.
77. Webster K.A., Discher D.J., Kaiser S., Hernandez O., Sato B., Bishopric N.H. Hypoxia-activated apoptosis of cardiac myocytes requires reoxygenation or a pH shift and is independent of p53. J Clin Invest. 104:1999;239-252. In this paper we demonstrate that p53 is completely dispensible for both hypoxia-induced and reoxygenation-induced apoptosis in the cardiac myocyte in vivo and in vitro, and that acidification is likely to be the trig myocyte in vivo and in vitro, and that acidification is likely to be the trigger for apoptosis during hypoxia.
78. Zhao Z.Q., Nakamura M., Wang N.P., Wilcox J.N., Shearer S., Ronson R.S., Guyton R.A., Vinten-Johansen J. Reperfusion induces myocardial apoptotic cell death. Cardiovasc Res. 45:2000;651-660.
79. Arola O.J., Saraste A., Pulkki K., Kallajoki M., Parvinen M., Voipio-Pulkki L.M. Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis. Cancer Res. 60:2000;1789-1792.
80. Kotamraju S., Konorev E.A., Joseph J., Kalyanaraman B. Doxorubicin- induced apoptosis in endothelial cells and cardiomyocytes is ameliorated by nitrone spin traps and ebselen - role of reactive oxygen and nitrogen species. J Biol Chem. 275:2000;33585-33592. This article demonstrates that oxidative stress lies upstream of cardiac myocyte apoptosis induced by doxorubicin, a widely used chemotherapeutic agent associated with cardiomyopathy.
81. Chen Q.M., Tu V.C., Wu Y., Bahl J.J. Hydrogen peroxide dose dependent induction of cell death or hypertrophy in cardiomyocytes. Arch Biochem Biophys. 373:2000;242-248.
82. Kang P.M., Haunstetter A., Aoki H., Usheva A., Izumo S. Morphological and molecular characterization of adult cardiomyocyte apoptosis during hypoxia and reoxygenation. Circ Res. 87:2000;118-125.
83. Hernandez O.M., Discher D.J., Bishopric N.H., Webster K.A. Rapid activation of neutral sphingomyelinase by hypoxia-reoxygenation of cardiac myocytes. Circ Res. 86:2000;198-204.
84. Arstall M.A., Sawyer D.B., Fukazawa R., Kelly R.A. Cytokine-mediated apoptosis in cardiac myocytes: the role of inducible nitric oxide synthase induction and peroxynitrite generation. Circ Res. 85:1999;829-840.
85. Pinsky D.J., Aji W., Szabolcs M., Athan E.S., Liu Y., Yang Y.M., Kline R.P., Olson K.E., Cannon P.J. Nitric oxide triggers programmed cell death (apoptosis) of adult rat ventricular myocytes in culture. Am J Physiol. 277:1999;H1189-H1199.
86. Brown G.C., Borutaite V. Nitric oxide, cytochrome c and mitochondria. Biochem Soc Symp. 66:1999;17-25.
87. Li J., Bombeck C.A., Yang S., Kim Y.M., Billiar T.R. Nitric oxide suppresses apoptosis via interrupting caspase activation and mitochondrial dysfunction in cultured hepatocytes. J Biol Chem. 274:1999;17325-17333.
88. Zech B., Wilm M., van Eldik R., Brune B. Mass spectrometric analysis of nitric oxide-modified caspase-3. J Biol Chem. 274:1999;20931-20936.
89. Weiland U., Haendeler J., Ihling C., Albus U., Scholz W., Ruetten H., Zeiher A.M., Dimmeler S. Inhibition of endogenous nitric oxide synthase potentiates ischemia-reperfusion-induced myocardial apoptosis via a caspase-3 dependent pathway. 45:2000;671-678.
90. Xuan Y.T., Tang X.L., Banerjee S., Takano H., Li R.C., Han H., Qiu Y., Li J.J., Bolli R. Nuclear factor-kappaB plays an essential role in the late phase of ischemic preconditioning in conscious rabbits. Circ Res. 84:1999;1095-1109.
91. Shinmura K., Tang X.L., Takano H., Hill M., Bolli R. Nitric oxide donors attenuate myocardial stunning in conscious rabbits. Am J Physiol. 277:1999;H2495-H2503.
92. Adderley S.R., Fitzgerald D.J. Glycoprotein IIb/IIIa antagonists induce apoptosis in rat cardiomyocytes by caspase-3 activation. J Biol Chem. 275:2000;5760-5766.
93. Holly T.A., Drincic A., Byun Y., Nakamura S., Harris K., Klocke F.J., Cryns V.L. Caspase inhibition reduces myocyte cell death induced by myocardial ischemia and reperfusion in vivo. J Mol Cell Cardiol. 31:1999;1709-1715.