Cardiomyocyte death in doxorubicin-induced cardiotoxicity

Archivum Immunologiae et Therapiae Experimentalis

Volumn 57, Issue 6, 2009, Pages 435-445

  Zhang, Yi Wei ^a,b   Shi, Jianjian ^a,b   Li, Yuan Jian ^b   Wei, Lei ^a  

^a INDIANA UNIVERSITY   (United States)

^b CENTRAL SOUTH UNIVERSITY   (China)

Author keywords

Apoptosis; Autophagy; Cardiomyocyte; Doxorubicin; Necrosis

Indexed keywords

DOXORUBICIN; REACTIVE OXYGEN METABOLITE;

APOPTOSIS; AUTOPHAGY; CANCER SURVIVOR; CARDIOMYOPATHY; CARDIOTOXICITY; CELL AGING; CELL DEATH; HEART MUSCLE CELL; HEART MUSCLE NECROSIS; HUMAN; NONHUMAN; REVIEW; SENESCENCE; SIGNAL TRANSDUCTION;

ANIMALS; CARDIOMYOPATHIES; CARDIOTOXINS; CELL AGING; CELL DEATH; DOXORUBICIN; HUMANS; MYOCYTES, CARDIAC; NEOPLASMS; REACTIVE OXYGEN SPECIES;

EID: 70450260555     PISSN: 0004069X     EISSN: 16614917     Source Type: Journal    
DOI: 10.1007/s00005-009-0051-8     Document Type: Review

References (123)

1. Y Aihara M Kurabayashi T Tanaka, et al. 2000 Doxorubicin represses CARP gene transcription through the generation of oxidative stress in neonatal rat cardiac myocytes: possible role of serine/threonine kinase-dependent pathways J Mol Cell Cardiol 32 1401 1414 10900167
2. AO Aliprantis RB Yang DS Weiss, et al. 2000 The apoptotic signaling pathway activated by Toll-like receptor-2 EMBO J 19 3325 3336 10880445
3. J An P Li J Li, et al. 2009 ARC is a critical cardiomyocyte survival switch in doxorubicin cardiotoxicity J Mol Med 87 401 410 19139834
4. A Aries P Paradis C Lefebvre, et al. 2004 Essential role of GATA-4 in cell survival and drug-induced cardiotoxicity Proc Natl Acad Sci USA 101 6975 6980 15100413
5. SC Armstrong 2004 Anti-oxidants and apoptosis: attenuation of doxorubicin induced cardiomyopathy by carvedilol J Mol Cell Cardiol 37 817 821 15380672
6. OJ Arola A Saraste K Pulkki, et al. 2000 Acute doxorubicin cardiotoxicity involves cardiomyocyte apoptosis Cancer Res 60 1789 1792 10766158
7. N Bahi J Zhang M Llovera, et al. 2006 Switch from caspasedependent to caspase-independent death during heart development: essential role of endonuclease G in ischemia-induced DNA processing of differentiated cardiomyocytes J Biol Chem 281 22943 22952 16754658
8. A Bast GR Haenen AM Bruynzeel, et al. 2007 Protection by flavonoids against anthracycline cardiotoxicity: from chemistry to clinical trials Cardiovasc Toxicol 7 154 159 17652822
9. RJ Bennink MJ VanDen Hoff FJ Van Hemert, et al. 2004 Annexin V imaging of acute doxorubicin cardiotoxicity (apoptosis) in rats J Nucl Med 45 842 848 15136635
10. MW Bergmann L Zelarayan C Gehrke 2008 Treatment-sensitive premature renal and heart senescence in hypertension Hypertension 52 61 62 18504325
11. D Bernhard G Laufer 2008 The aging cardiomyocyte: a mini-review Gerontology 54 24 31 18196923
12. F Bernuzzi S Recalcati A Alberghini, et al. 2009 Reactive oxygen species-independent apoptosis in doxorubicin-treated H9c2 cardiomyocytes: role for heme oxygenase-1 down-modulation Chem Biol Interact 177 12 20 18845130
13. AM Bruynzeel El Abou MA Hassan E Torun, et al. 2007 Caspase-dependent and -independent suppression of apoptosis by monoHER in Doxorubicin treated cells Br J Cancer 96 450 456 17285121
14. DH Burgess M Svensson T Dandrea, et al. 1999 Human skeletal muscle cytosols are refractory to cytochrome c-dependent activation of type-II caspases and lack APAF-1 Cell Death Differ 6 256 261 10200576
15. DJ Burkhart BL Barthel GC Post, et al. 2006 Design, synthesis, and preliminary evaluation of doxazolidine carbamates as prodrugs activated by carboxylesterases J Med Chem 49 7002 7012 17125253
16. C Camello-Almaraz PJ Gomez-Pinilla MJ Pozo, et al. 2006 Mitochondrial reactive oxygen species and Ca2+ signaling Am J Physiol Cell Physiol 291 C1082 1088 16760264
17. TM Casey PG Arthur MA Bogoyevitch 2007 Necrotic death without mitochondrial dysfunction-delayed death of cardiac myocytes following oxidative stress Biochim Biophys Acta 1773 342 351 17207543
18. J Chang M Xie VR Shah, et al. 2006 Activation of Rho-associated coiled-coil protein kinase 1 (ROCK-1) by caspase-3 cleavage plays an essential role in cardiac myocyte apoptosis Proc Natl Acad Sci USA 103 14495 14500 16983089
19. AC Childs SL Phaneuf AJ Dirks, et al. 2002 Doxorubicin treatment in vivo causes cytochrome C release and cardiomyocyte apoptosis, as well as increased mitochondrial efficiency, superoxide dismutase activity, and Bcl-2:Bax ratio Cancer Res 62 4592 4598 12183413
20. CC Chua X Liu J Gao, et al. 2006 Multiple actions of pifithrin-alpha on doxorubicin-induced apoptosis in rat myoblastic H9c2 cells Am J Physiol Heart Circ Physiol. 290 H2606 2613 16687611
21. BJ Cusack B Musser H Gambliel, et al. 2003 Effect of dexrazoxane on doxorubicin pharmacokinetics in young and old rats Cancer Chemother Pharmacol 51 139 146 12647015
22. De D'Anglemont A Tassigny R Souktani P Henry, et al. 2004 Volume-sensitive chloride channels (ICl,vol) mediate doxorubicin-induced apoptosis through apoptotic volume decrease in cardiomyocytes Fundam Clin Pharmacol 18 531 538
23. S Davani F Deschaseaux D Chalmers, et al. 2005 Can stem cells mend a broken heart? Cardiovasc Res 65 305 316 15639469
24. GR De Meyer W Martinet 2008 Autophagy in the cardiovascular system Biochim Biophys Acta 1793 1485 1495 19152812
25. A Deniaud El Sharaf O Dein E Maillier, et al. 2008 Endoplasmic reticulum stress induces calcium-dependent permeability transition, mitochondrial outer membrane permeabilization and apoptosis Oncogene 27 285 299 17700538
26. A Diwan SJ Matkovich Q Yuan, et al. 2009 Endoplasmic reticulum- mitochondria crosstalk in NIX-mediated murine cell death J Clin Invest 119 203 212 19065046
27. 2nd Dorn GW 2009 Apoptotic and non-apoptotic programmed cardiomyocyte death in ventricular remodelling Cardiovasc Res 81 465 473 18779231
28. GC Fan X Zhou X Wang, et al. 2008 Heat shock protein 20 interacting with phosphorylated Akt reduces doxorubicin-triggered oxidative stress and cardiotoxicity Circ Res 103 1270 1279 18948619
29. PW Fisher F Salloum A Das, et al. 2005 Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity Circulation 111 1601 1610 15811867
30. W Gen M Tani J Takeshita, et al. 2001 Mechanisms of Ca2+ overload induced by extracellular H2O2 in quiescent isolated rat cardiomyocytes Basic Res Cardiol 96 623 629 11770081
31. L Gianni EH Herman SE Lipshultz, et al. 2008 Anthracycline cardiotoxicity: from bench to bedside J Clin Oncol 26 3777 3784 18669466
32. AB Gustafsson RA Gottlieb 2008 Heart mitochondria: gates of life and death Cardiovasc Res 77 334 343 18006487
33. AB Gustafsson RA Gottlieb 2009 Autophagy in ischemic heart disease Circ Res 104 150 158 19179668
34. ML Hensley KL Hagerty T Kewalramani, et al. 2009 American Society of Clinical Oncology 2008 clinical practice guideline update: use of chemotherapy and radiation therapy protectants J Clin Oncol 27 127 145 19018081
35. M Hoyer-Hansen L Bastholm P Szyniarowski, et al. 2007 Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-beta, and Bcl-2 Mol Cell 25 193 205 17244528
36. D Iarussi P Indolfi F Casale, et al. 2001 Recent advances in the prevention of anthracycline cardiotoxicity in childhood Curr Med Chem 8 1649 1660 11562284
37. E Ikegami R Fukazawa M Kanbe, et al. 2007 Edaravone, a potent free radical scavenger, prevents anthracycline-induced myocardial cell death Circ J 71 1815 1820 17965508
38. T Ito Y Fujio K Takahashi, et al. 2007 Degradation of NFAT5, a transcriptional regulator of osmotic stress-related genes, is a critical event for doxorubicin-induced cytotoxicity in cardiac myocytes J Biol Chem 282 1152 1160 17105721
39. M Jang Y S Kendaiah B Drew, et al. 2004 Doxorubicin treatment in vivo activates caspase-12 mediated cardiac apoptosis in both male and female rats FEBS Lett 577 483 490 15556633
40. R Jeyaseelan C Poizat RK Baker, et al. 1997 A novel cardiac- restricted target for doxorubicin. CARP, a nuclear modulator of gene expression in cardiac progenitor cells and cardiomyocytes J Biol Chem 272 22800 22808 9278441
41. J Kajstura M Rota K Urbanek, et al. 2006 The telomere-telomerase axis and the heart Antioxid Redox Signal 8 2125 2141 17034355
42. SV Kalivendi EA Konorev S Cunningham, et al. 2005 Doxorubicin activates nuclear factor of activated T-lymphocytes and Fas ligand transcription: role of mitochondrial reactive oxygen species and calcium Biochem J 389 527 539 15799720
43. T Kawamura K Hasegawa T Morimoto, et al. 2004 Expression of p300 protects cardiac myocytes from apoptosis in vivo Biochem Biophys Res Commun 315 733 738 14975762
44. M Khan S Varadharaj JC Shobha, et al. 2006 C-phycocyanin ameliorates doxorubicin-induced oxidative stress and apoptosis in adult rat cardiomyocytes J Cardiovasc Pharmacol 47 9 20 16424780
45. DS Kim HR Kim ER Woo, et al. 2005 Inhibitory effects of rosmarinic acid on adriamycin-induced apoptosis in H9c2 cardiac muscle cells by inhibiting reactive oxygen species and the activations of c-Jun N-terminal kinase and extracellular signal-regulated kinase Biochem Pharmacol 70 1066 1078 16102732
46. DS Kim ER Woo SW Chae, et al. 2007 Plantainoside D protects adriamycin-induced apoptosis in H9c2 cardiac muscle cells via the inhibition of ROS generation and NF-kappaB activation Life Sci 80 314 323 17034819
47. SY Kim SJ Kim BJ Kim, et al. 2006 Doxorubicin-induced reactive oxygen species generation and intracellular Ca2+ increase are reciprocally modulated in rat cardiomyocytes Exp Mol Med 38 535 545 17079870
48. Y Kim AG Ma K Kitta, et al. 2003 Anthracycline-induced suppression of GATA-4 transcription factor: implication in the regulation of cardiac myocyte apoptosis Mol Pharmacol 63 368 377 12527808
49. J Kluza P Marchetti MA Gallego, et al. 2004 Mitochondrial proliferation during apoptosis induced by anticancer agents: effects of doxorubicin and mitoxantrone on cancer and cardiac cells Oncogene 23 7018 7030 15273722
50. EA Konorev S Vanamala B Kalyanaraman 2008 Differences in doxorubicin-induced apoptotic signaling in adult and immature cardiomyocytes Free Radic Biol Med 45 1723 1728 18926904
51. S Kotamraju EA Konorev J Joseph, et al. 2000 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 33585 33592 10899161
52. F Kratz G Ehling HM Kauffmann, et al. 2007 Acute and repeat-dose toxicity studies of the (6-maleimidocaproyl)hydrazone derivative of doxorubicin (DOXO-EMCH), an albumin-binding prodrug of the anticancer agent doxorubicin Hum Exp Toxicol 26 19 35 17334177
53. T L'Ecuyer S Sanjeev R Thomas, et al. 2006 DNA damage is an early event in doxorubicin-induced cardiac myocyte death Am J Physiol Heart Circ Physiol 291 H1273 280 16565313
54. D Lebrecht A Geist UP Ketelsen, et al. 2007 The 6-maleimidocaproyl hydrazone derivative of doxorubicin (DOXO-EMCH) is superior to free doxorubicin with respect to cardiotoxicity and mitochondrial damage Int J Cancer 120 927 934 17131338
55. D Lebrecht A Geist UP Ketelsen, et al. 2007 Dexrazoxane prevents doxorubicin-induced long-term cardiotoxicity and protects myocardial mitochondria from genetic and functional lesions in rats Br J Pharmacol 151 771 778 17519947
56. D Lebrecht UA Walker 2007 Role of mtDNA lesions in anthracycline cardiotoxicity Cardiovasc Toxicol 7 108 113 17652814
57. B Levine S Sinha G Kroemer 2008 Bcl-2 family members: dual regulators of apoptosis and autophagy Autophagy 4 600 606 18497563
58. H Li H Gu B Sun 2007 Protective effects of pyrrolidine dithiocarbamate on myocardium apoptosis induced by adriamycin in rats Int J Cardiol 114 159 165 16712983
59. J Li PR Gwilt 2003 The effect of age on the early disposition of doxorubicin Cancer Chemother Pharmacol 51 395 402 12679882
60. K Li RY Sung WZ Huang, et al. 2006 Thrombopoietin protects against in vitro and in vivo cardiotoxicity induced by doxorubicin Circulation 113 2211 2220 16651473
61. CC Lim C Zuppinger X Guo, et al. 2004 Anthracyclines induce calpain-dependent titin proteolysis and necrosis in cardiomyocytes J Biol Chem 279 8290 8299 14676206
62. SE Lipshultz SD Colan RD Gelber, et al. 1991 Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood N Engl J Med 324 808 815 1997853
63. J Liu W Mao B Ding, et al. 2008 ERKs/p53 signal transduction pathway is involved in doxorubicin-induced apoptosis in H9c2 cells and cardiomyocytes Am J Physiol Heart Circ Physiol 295 H1956 1965 18775851
64. X Liu Z Chen CC Chua, et al. 2002 Melatonin as an effective protector against doxorubicin-induced cardiotoxicity Am J Physiol Heart Circ Physiol 283 H254 263 12063298
65. X Liu CC Chua J Gao, et al. 2004 Pifithrin-alpha protects against doxorubicin-induced apoptosis and acute cardiotoxicity in mice Am J Physiol Heart Circ Physiol 286 H933 939 14766674
66. H Lou I Danelisen PK Singal 2005 Involvement of mitogen-activated protein kinases in adriamycin-induced cardiomyopathy Am J Physiol Heart Circ Physiol 288 H1925 1930 15772336
67. V Machado A Cabral P Monteiro, et al. 2008 Carvedilol as a protector against the cardiotoxicity induced by anthracyclines (doxorubicin) Rev Port Cardiol 27 1277 1296 19178029
68. SD Madden M Donovan TG Cotter 2007 Key apoptosis regulating proteins are down-regulated during postnatal tissue development Int J Dev Biol 51 415 423 17616931
69. Y Maejima S Adachi H Ito, et al. 2008 Induction of premature senescence in cardiomyocytes by doxorubicin as a novel mechanism of myocardial damage Aging Cell 7 125 136 18031568
70. Y Maejima S Adachi K Morikawa, et al. 2005 Nitric oxide inhibits myocardial apoptosis by preventing caspase-3 activity via S-nitrosylation J Mol Cell Cardiol 38 163 174 15623433
71. MC Maiuri E Zalckvar A Kimchi, et al. 2007 Self-eating and self-killing: crosstalk between autophagy and apoptosis Nat Rev Mol Cell Biol 8 741 752 17717517
72. Y Matsui S Kyoi H Takagi, et al. 2008 Molecular mechanisms and physiological significance of autophagy during myocardial ischemia and reperfusion Autophagy 4 409 415 18227645
73. I Mercier M Vuolo R Madan, et al. 2005 ARC, an apoptosis suppressor limited to terminally differentiated cells, is induced in human breast cancer and confers chemo- and radiation-resistance Cell Death Differ 12 682 686 15861191
74. A Mijares JR Lopez 2001 L-carnitine prevents increase in diastolic [CA2+] induced by doxorubicin in cardiac cells Eur J Pharmacol 425 117 120 11502276
75. P Mukhopadhyay S Batkai M Rajesh, et al. 2007 Pharmacological inhibition of CB1 cannabinoid receptor protects against doxorubicin-induced cardiotoxicity J Am Coll Cardiol 50 528 536 17678736
76. JA Munoz-Gamez JM Rodriguez-Vargas R Quiles-Perez, et al. 2009 PARP-1 is involved in autophagy induced by DNA damage Autophagy 5 61 74 19001878
77. T Nakamura Y Ueda Y Juan, et al. 2000 Fas-mediated apoptosis in adriamycin-induced cardiomyopathy in rats: In vivo study Circulation 102 572 578 10920071
78. TG Neilan SL Blake F Ichinose, et al. 2007 Disruption of nitric oxide synthase 3 protects against the cardiac injury, dysfunction, and mortality induced by doxorubicin Circulation 116 506 514 17638931
79. K Nishida S Kyoi O Yamaguchi, et al. 2009 The role of autophagy in the heart Cell Death Differ 16 31 38 19008922
80. K Nishida O Yamaguchi K Otsu 2008 Crosstalk between autophagy and apoptosis in heart disease Circ Res 103 343 351 18703786
81. J Nitobe S Yamaguchi M Okuyama, et al. 2003 Reactive oxygen species regulate FLICE inhibitory protein (FLIP) and susceptibility to Fas-mediated apoptosis in cardiac myocytes Cardiovasc Res 57 119 128 12504821
82. J Niu A Azfer K Wang, et al. 2009 Cardiac-targeted expression of soluble Fas attenuates doxorubicin-induced cardiotoxicity in mice J Pharmacol Exp Ther 328 740 748 19066339
83. N Nozaki T Shishido Y Takeishi, et al. 2004 Modulation of doxorubicin-induced cardiac dysfunction in toll-like receptor-2-knockout mice Circulation 110 2869 2874 15505089
84. V Parra V Eisner M Chiong, et al. 2008 Changes in mitochondrial dynamics during ceramide-induced cardiomyocyte early apoptosis Cardiovasc Res 77 387 397 18006463
85. CA Piantadosi MS Carraway A Babiker, et al. 2008 Heme oxygenase-1 regulates cardiac mitochondrial biogenesis via Nrf2-mediated transcriptional control of nuclear respiratory factor-1 Circ Res 103 1232 1240 18845810
86. C Poizat PL Puri Y Bai, et al. 2005 Phosphorylation-dependent degradation of p300 by doxorubicin-activated p38 mitogen-activated protein kinase in cardiac cells Mol Cell Biol 25 2673 2687 15767673
87. A Riad S Bien D Westermann, et al. 2009 Pretreatment with statin attenuates the cardiotoxicity of Doxorubicin in mice Cancer Res 69 695 699 19147586
88. L Rigacci S Mappa L Nassi, et al. 2007 Liposome-encapsulated doxorubicin in combination with cyclophosphamide, vincristine, prednisone and rituximab in patients with lymphoma and concurrent cardiac diseases or pre-treated with anthracyclines Hematol Oncol 25 198 203 17654614
89. BA Rothermel JA Hill 2008 Autophagy in load-induced heart disease Circ Res 103 1363 1369 19059838
90. DC Rubinsztein M Difiglia N Heintz, et al. 2005 Autophagy and its possible roles in nervous system diseases, damage and repair Autophagy 1 11 22 16874045
91. E Salvatorelli P Menna M Lusini, et al. 2009 Doxorubicinolone formation and efflux: a salvage pathway against epirubicin accumulation in human heart J Pharmacol Exp Ther 329 175 184 19144686
92. D Sanchis M Mayorga M Ballester, et al. 2003 Lack of Apaf-1 expression confers resistance to cytochrome c-driven apoptosis in cardiomyocytes Cell Death Differ 10 977 986 12934072
93. D Schmid C Munz 2007 Innate and adaptive immunity through autophagy Immunity 27 11 21 17663981
94. J Shi L Wei 2007 Rho kinase in the regulation of cell death and survival Arch Immunol Ther Exp 55 61 75
95. S Shimizu T Kanaseki N Mizushima, et al. 2004 Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes Nat Cell Biol 6 1221 1228 15558033
96. H Shimomura F Terasaki T Hayashi, et al. 2001 Autophagic degeneration as a possible mechanism of myocardial cell death in dilated cardiomyopathy Jpn Circ J 65 965 968 11716248
97. Y Shizukuda S Matoba OY Mian, et al. 2005 Targeted disruption of p53 attenuates doxorubicin-induced cardiac toxicity in mice Mol Cell Biochem 273 25 32 16013437
98. PK Singal N Iliskovic 1998 Doxorubicin-induced cardiomyopathy N Engl J Med 339 900 905 9744975
99. LE Solem LJ Heller KB Wallace 1996 Dose-dependent increase in sensitivity to calcium-induced mitochondrial dysfunction and cardiomyocyte cell injury by doxorubicin J Mol Cell Cardiol 28 1023 1032 8762040
100. P Spallarossa P Fabbi V Manca, et al. 2005 Doxorubicin-induced expression of LOX-1 in H9c2 cardiac muscle cells and its role in apoptosis Biochem Biophys Res Commun 335 188 196 16055083
101. P Spallarossa S Garibaldi P Altieri, et al. 2004 Carvedilol prevents doxorubicin-induced free radical release and apoptosis in cardiomyocytes in vitro J Mol Cell Cardiol 37 837 846 15380674
102. HB Suliman MS Carraway AS Ali, et al. 2007 The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy J Clin Invest 117 3730 3741 18037988
103. G Takemura H Fujiwara 2007 Doxorubicin-induced cardiomyopathy from the cardiotoxic mechanisms to management Prog Cardiovasc Dis 49 330 352 17329180
104. E Tatlidede O Sehirli A Velioglu-Ogunc, et al. 2009 Resveratrol treatment protects against doxorubicin-induced cardiotoxicity by alleviating oxidative damage Free Radic Res 43 195 205 19169920
105. A Terman UT Brunk 2005 Autophagy in cardiac myocyte homeostasis, aging, and pathology Cardiovasc Res 68 355 365 16213475
106. A Terman B Gustafsson UT Brunk 2006 The lysosomal-mitochondrial axis theory of postmitotic aging and cell death Chem Biol Interact 163 29 37 16737690
107. Y Tsujimoto S Shimizu 2005 Another way to die: autophagic programmed cell death Cell Death Differ. 12 suppl 2 1528 1534 16247500
108. DD Von Hoff M Rozencweig M Layard, et al. 1977 Daunomycin-induced cardiotoxicity in children and adults. A review of 110 cases Am J Med 62 200 208 835599
109. KB Wallace 2003 Doxorubicin-induced cardiac mitochondrionopathy Pharmacol Toxicol 93 105 115 12969434
110. KB Wallace 2007 Adriamycin-induced interference with cardiac mitochondrial calcium homeostasis Cardiovasc Toxicol 7 101 107 17652813
111. GW Wang JB Klein YJ. Kang 2001 Metallothionein inhibits doxorubicin-induced mitochondrial cytochrome c release and caspase-3 activation in cardiomyocytes J Pharmacol Exp Ther 298 461 468 11454906
112. S Wang S Kotamraju E Konorev, et al. 2002 Activation of nuclear factor-kappaB during doxorubicin-induced apoptosis in endothelial cells and myocytes is pro-apoptotic: the role of hydrogen peroxide Biochem J 367 729 740 12139490
113. AG Yakovlev K Ota G Wang, et al. 2001 Differential expression of apoptotic protease-activating factor-1 and caspase-3 genes and susceptibility to apoptosis during brain development and after traumatic brain injury J Neurosci 21 7439 7446 11567033
114. C Yan B Ding T Shishido, et al. 2007 Activation of extracellular signal-regulated kinase 5 reduces cardiac apoptosis and dysfunction via inhibition of a phosphodiesterase 3A/inducible cAMP early repressor feedback loop Circ Res 100 510 519 17272811
115. ET Yeh AT Tong DJ Lenihan, et al. 2004 Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management Circulation 109 3122 3131 15226229
116. Y Yildirim E Gultekin ME Avci, et al. 2008 Cardiac safety profile of pegylated liposomal doxorubicin reaching or exceeding lifetime cumulative doses of 550 mg/m2 in patients with recurrent ovarian and peritoneal cancer Int J Gynecol Cancer 18 223 227 17511800
117. T Yorimitsu DJ Klionsky 2005 Autophagy: molecular machinery for self-eating Cell Death Differ 12 suppl 2 1542 1552 16247502
118. Q Zeng Q Zhou F Yao, et al. 2008 Endothelin-1 regulates cardiac L-type calcium channels via NAD(P)H oxidase-derived superoxide J Pharmacol Exp Ther 326 732 738 18539650
119. S Zhou A Starkov MK Froberg, et al. 2001 Cumulative and irreversible cardiac mitochondrial dysfunction induced by doxorubicin Cancer Res 61 771 777 11212281
120. W Zhu W Shou RM Payne, et al. 2008 A mouse model for juvenile doxorubicin-induced cardiac dysfunction Pediatr Res 64 488 494 18614963
121. W Zhu MH Soonpaa H Chen 2009 Acute doxorubicin cardiotoxicity is associated with p53-induced inhibition of the mammalian target of rapamycin pathway Circulation 119 99 106 19103993
122. AV Zima LA Blatter 2006 Redox regulation of cardiac calcium channels and transporters Cardiovasc Res 71 310 321 16581043
123. Y Zou S Evans J Chen, et al. 1997 CARP, a cardiac ankyrin repeat protein, is downstream in the Nkx2-5 homeobox gene pathway Development 124 793 804 9043061