Molecular mechanisms of toxicity of simvastatin, widely used cholesterol-lowering drug. A review

Central European Journal of Medicine

Volumn 5, Issue 3, 2010, Pages 269-279

  Kaminsky, Yury G ^a   Kosenko, Elena A ^a  

^a INSTITUTE OF THEORETICAL AND EXPERIMENTAL BIOPHYSICS   (Russian Federation)

Author keywords

Mitochondria; Simvastatin; Statins; Toxicity

Indexed keywords

CARVEDILOL; CHLORZOXAZONE; CYCLOSPORIN; DILTIAZEM; EZETIMIBE PLUS SIMVASTATIN; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE; METHYLPREDNISOLONE; MEVALONIC ACID; PRAVASTATIN; PROPOFOL; RANOLAZINE; SIMVASTATIN; UBIDECARENONE; UBIQUINONE;

ACUTE KIDNEY FAILURE; CELL DEATH; CHOLESTATIC HEPATITIS; CYTOTOXICITY; DNA DAMAGE; DNA FRAGMENTATION; DNA SYNTHESIS INHIBITION; DRUG SAFETY; DRUG SUBSTITUTION; DRUG WITHDRAWAL; EXERCISE TOLERANCE; FATTY ACID OXIDATION; HUMAN; HYPERCHOLESTEROLEMIA; HYPERLIPIDEMIA; LACTATE BLOOD LEVEL; LACTIC ACIDOSIS; LIVER FAILURE; LIVER TOXICITY; MEMBRANE DEPOLARIZATION; MITOCHONDRIAL ENERGY TRANSFER; MITOCHONDRIAL RESPIRATION; MUSCLE CRAMP; MUSCLE FATIGUE; MUSCLE NECROSIS; MYALGIA; NONHUMAN; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PANCREATITIS; PRIORITY JOURNAL; REVIEW; RHABDOMYOLYSIS; SIDE EFFECT; TENDINITIS;

EID: 77952889820     PISSN: 18951058     EISSN: 16443640     Source Type: Journal    
DOI: 10.2478/s11536-009-0123-5     Document Type: Review

References (77)

1. M. Evans A. Rees 2002 Effects of HMG-CoA reductase inhibitors on skeletal muscle: are all statins the same? Drug Saf. 25 649 663 10.2165/00002018- 200225090-00004 1:CAS:528:DC%2BD38XntFektLg%3D 12137559
2. D.M. Kent 2006 Stroke - An Equal Opportunity for the Initiation of Statin Therapy N. Engl. J. Med. 355 613 5 10.1056/NEJMe068146 1:CAS:528: DC%2BD28XotVKlsb0%3D 16899782 (Pubitemid 44200655)
3. D.R. Illingworth 1988 An overview of lipid-lowering drugs Drugs 36 Suppl3 63 71 10.2165/00003495-198800363-00015 1:CAS:528:DyaL1MXkvV2mu7k%3D 3076124
4. J.F. Walker 1988 HMG CoA reductase inhibitors, Current clinical experience Drugs 36 Suppl3 83 6 10.2165/00003495-198800363-00017 3076126
5. Z. Qiao J. Ren H. Chen 2009 Simvastatin reduces expression and activity of lipoprotein-associated phospholipase A(2) in the aorta of hypercholesterolaemic atherosclerotic rabbits J. Int. Med. Res. 37 1029 37 1:CAS:528:DC%2BD1MXhtlynsbvI 19761685
6. R. Corti J.I. Osende J.T. Fallon V. Fuster G. Mizsei H. Jneid, et al. 2004 The selective peroxisomal proliferator-activated receptor-gamma agonist has an additive effect on plaque regression in combination with simvastatin in experimental atherosclerosis: in vivo study by high-resolution magnetic resonance imaging J. Am. Coll. Cardiol. 43 464 73 10.1016/j.jacc.2003.08.048 1:CAS:528:DC%2BD2cXitV2jtbY%3D 15013132 (Pubitemid 38167710)
7. N. Werner S. Kosiol T. Schiegl P. Ahlers K. Walenta A. Link, et al. 2005 Circulating Endothelial Progenitor Cells and Cardiovascular Outcomes N. Engl. J. Med. 353 999 1007 10.1056/NEJMoa043814 1:CAS:528:DC%2BD2MXpvVOisbw%3D 16148285 (Pubitemid 41262334)
8. A.J. Dirks K.M. Jones 2006 Statin-induced apoptosis and skeletal myopathy Am. J. Physiol. Cell Physiol. 291 C1208 12 10.1152/ajpcell.00226.2006 1:CAS:528:DC%2BD2sXjvVKq 16885396 (Pubitemid 44878591)
9. D.J. Maron S. Fazio M.F. Linton 2000 Current perspectives on statins Circulation 101 207 13 1:CAS:528:DC%2BD3cXptFKlug%3D%3D 10637210
10. W. Palinski C. Napoli 2002 Unraveling pleiotropic effects of statins on plaque rupture Arterioscler. Thromb. Vasc. Biol. 22 1745 50 10.1161/01.ATV. 0000038754.39483.CD 1:CAS:528:DC%2BD38XpsVyqtr4%3D 12426197 (Pubitemid 35315755)
11. M. Manzoni M. Rollini 2002 Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs Appl. Microbiol. Biotechnol. 58 555 64 10.1007/s00253-002-0932-9 1:CAS:528:DC%2BD38Xjs12ktL0%3D 11956737 (Pubitemid 34299219)
12. M. Schachter 2005 Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update Fundam. Clin. Pharmacol. 19 117 25 10.1111/j.1472-8206.2004.00299.x 1:CAS:528:DC%2BD2MXhsVCms7Y%3D 15660968 (Pubitemid 40204354)
13. J. Shepherd 2006 Who should receive a statin these days? Lessons from recent clinical trials J. Intern. Med. 260 305 9 10.1111/j.1365-2796.2006.01700. x 1:CAS:528:DC%2BD28Xht1WntLfF 16961668 (Pubitemid 44370904)
14. P. Sirvent J. Mercier G. Vassort A. Lacampagne 2005 Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle Biochem. Biophys. Res. Commun. 329 1067 75 10.1016/j.bbrc.2005.02.070 1:CAS:528:DC%2BD2MXitVChtbY%3D 15752763 (Pubitemid 40341384)
15. MRC/BHF Heart Protection Study Collaborative Group J. Armitage L. Bowman R. Collins S. Parish J. Tobert 2009 Effects of simvastatin 40 mg daily on muscle and liver adverse effects in a 5-year randomized placebo-controlled trial in 20,536 highrisk people BMC Clin. Pharmacol. 9 6 10.1186/1471-2210-9-6 19442259
16. A.K. Goli S.A. Goli R.P. Byrd T.M. Roy 2002 Simvastatin-induced lactic acidosis: a rare adverse reaction? Clin. Pharmacol. Ther. 72 461 4 10.1067/mcp.2002.127943 12386648 (Pubitemid 35178871)
17. P.D. Thompson P. Clarkson R.H. Karas 2003 Statin-associated myopathy JAMA 289 1681 90 10.1001/jama.289.13.1681 1:CAS:528:DC%2BD3sXisF2is7k%3D 12672737 (Pubitemid 37430274)
18. C.V. Venero P.D. Thompson 2009 Managing statin myopathy Endocrinol. Metab. Clin. North. Am. 38 121 36 10.1016/j.ecl.2008.11.002 1:CAS:528: DC%2BD1MXkt1eks7w%3D 19217515
19. M.A. Omar J.P. Wilson 2002 FDA adverse event reports on statin-associated rhabdomyolysis Ann. Pharmacother. 36 288 95 10.1345/aph.1A289 1:CAS:528:DC%2BD38XitFOjtLg%3D 11847951
20. J.A. Staffa J. Chang L. Green 2002 Cerivastatin and reports of fatal rhabdomyolysis N. Engl. J. Med. 346 539 40 10.1056/NEJM200202143460721 11844864
21. M. Ballarè M. Campanini G. Airoldi G. Zaccala M.C. Bertoncelli G. Cornaglia, et al. 1992 Hepatotoxicity of hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors Minerva Gastroenterol. Dietol. 38 41 4 1520752
22. A. Waness S. Bahlas S. Al Shohaib 2008 Simvastatin-induced rhabdomyolysis and acute renal injury Blood Purif. 26 394 8 10.1159/000141931 1:CAS:528:DC%2BD1cXptVygsr4%3D 18594138
23. F.A. Qari 2009 Severe rhabdomyolysis and acute renal failure secondary to use of simvastatin in undiagnosed hypothyroidism Saudi J. Kidney Dis. Transpl. 20 127 9 19112232
24. I. Marie H. Delafenêtre N. Massy C. Thuillez C. Noblet Network of the French Pharmacovigilance Centers 2008 Tendinous disorders attributed to statins: a study on ninety-six spontaneous reports in the period 1990-2005 and review of the literature Arthritis Rheum. 59 367 72 10.1002/art.23309 1:CAS:528:DC%2BD1cXkt1yltLg%3D 18311771 (Pubitemid 351399207)
25. J. Bae J.A. Jarcho M.D. Denton C.C. Magee 2002 Statin specific toxicity in organ transplant recipients: case report and review of the literature J. Nephrol. 15 317 9 12113605
26. T. Evangelista J. Ferro P. Pereira M. de Carvalho 2009 A case of asymptomatic cytoplasmic body myopathy revealed by sinvastatin Neuromuscul. Disord. 19 66 8 10.1016/j.nmd.2008.10.008 19084404
27. S. Tuteja N.T. Pyrsopoulos W.R. Wolowich K. Khanmoradi D.M. Levi G. Selvaggi, et al. 2008 Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation Pharmacotherapy 28 1188 93 10.1592/phco.28.9.1188 18752389
28. N. Kanathur M.G. Mathai R.P. Byrd C.L. Fields T.M. Roy 2001 Simvastatin-diltiazem drug interaction resulting in rhabdomyolysis and hepatitis Tenn. Med. 94 339 41 1:STN:280:DC%2BD3MrgtFekuw%3D%3D 11550401
29. J.L. Johnson I.B. Loomis 2006 A case of simvastatin-associated pancreatitis and review of statin-associated pancreatitis Pharmacotherapy 26 414 22 10.1592/phco.26.3.414 16503723
30. S. Singh Y.K. Loke 2006 Statins and pancreatitis: a systematic review of observational studies and spontaneous case reports Drug Saf. 29 1123 32 10.2165/00002018-200629120-00004 1:CAS:528:DC%2BD2sXhtVCmsrs%3D 17147459 (Pubitemid 44904828)
31. J.W. Bielecki C. Schraner V. Briner M. Kuhn 1999 Rhabdomyolysis and cholestatic hepatitis under treatment with simvastatin and chlorzoxazone Schweiz. Med. Wochenschr. 129 514 8 1:STN:280:DyaK1M3lsFyktw%3D%3D 10322565
32. S.I. Rifkin 2008 Multiple drug interactions in a renal transplant patient leading to simvastatin-induced rhabdomyolysis: a case report Medscape J. Med. 10 264 19099014
33. L. Francis E. Bonilla E. Soforo H. Neupane H. Nakhla C. Fuller, et al. 2008 Fatal toxic myopathy attributed to propofol, methylprednisolone, and cyclosporine after prior exposure to colchicine and simvastatin Clin. Rheumatol. 27 129 31 10.1007/s10067-007-0696-9 17628739 (Pubitemid 350182692)
34. K. Nakahara M. Kuriyama Y. Sonoda H. Yoshidome H. Nakagawa J. Fujiyama, et al. 1998 Myopathy induced by HMG-CoA reductase inhibitors in rabbits: a pathological, electrophysiological, and biochemical study Toxicol. Appl. Pharmacol. 152 99 106 10.1006/taap.1998.8491 1:CAS:528:DyaK1cXmsl2gsrg%3D 9772205 (Pubitemid 28498678)
35. F.R. Westwood A. Bigley K. Randall A.M. Marsden R.C. Scott 2005 Statin-induced muscle necrosis in the rat: distribution, development, and fibre selectivity Toxicol. Pathol. 33 246 57 10.1080/01926230590908213 1:CAS:528:DC%2BD2MXitV2hs7g%3D 15902968 (Pubitemid 40381453)
36. S.H. Baytan M. Alkanat M. Okuyan M. Ekinci E. Gedikli M. Ozeren 2008 Simvastatin impairs spatial memory in rats at a specific dose level Tohoku J. Exp. Med. 214 341 9 10.1620/tjem.214.341 1:CAS:528:DC%2BD1cXmsV2iur4%3D 18441510 (Pubitemid 351761052)
37. P. Oms N. Assie F. Bruniquel A.D. Degryse G. van Haverbeke A. Delhon 1995 Biochemical changes and morphological alterations of liver and kidney in hamsters after administration of the HMG-coenzyme A reductase inhibitor, simvastatin: prevention and reversibility by mevalonate Pharmacol. Toxicol. 77 391 6 10.1111/j.1600-0773.1995.tb01048.x 1:CAS:528:DyaK2MXpvV2ltbg%3D 8835365
38. R.J. Cenedella A.R. Neely P. Sexton 2005 Concentration and distribution of ubiquinone (coenzyme Q), the endogenous lipid antioxidant, in the rat lens: effect of treatment with simvastatin Mol. Vis. 11 594 602 1:CAS:528: DC%2BD28XitFemsbY%3D 16110301
39. J. Sacher L. Weigl M. Werner C. Szegedi M. Hohenegger 2005 Delineation of myotoxicity induced by 3-hydroxy-3-methylglutaryl CoA reductase inhibitors in human skeletal muscle cells J. Pharmac. Exp. Ther. 314 1032 41 10.1124/jpet.105.086462 1:CAS:528:DC%2BD2MXpvFSqsro%3D (Pubitemid 41205966)
40. S. Demyanets C. Kaun S. Pfaffenberger P.J. Hohensinner G. Rega J. Pammer, et al. 2006 Hydroxymethylglutaryl-coenzyme A reductase inhibitors induce apoptosis in human cardiac myocytes in vitro Biochem. Pharmacol. 71 1324 30 10.1016/j.bcp.2006.01.016 1:CAS:528:DC%2BD28XivVOjsbc%3D 16540096
41. P. Cafforio F. Dammacco A. Gernone F. Silvestris 2005 Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells Carcinogenesis 26 883 91 10.1093/carcin/bgi036 1:CAS:528:DC%2BD2MXjsFOmsrg%3D 15705602 (Pubitemid 41214316)
42. K. Boucher C.S. Siegel P. Sharma P.V. Hauschka K.R. Solomon 2006 HMG-CoA reductase inhibitors induce apoptosis in pericytes Microvasc. Res. 71 91 102 10.1016/j.mvr.2005.11.007 1:CAS:528:DC%2BD28XjvVGlsrY%3D 16427097
43. K. Yokota F. Miyoshi T. Miyazaki K. Sato Y. Yoshida Y. Asanuma, et al. 2008 High concentration simvastatin induces apoptosis in fibroblast-like synoviocytes from patients with rheumatoid arthritis J. Rheumatol. 35 193 200 1:CAS:528:DC%2BD1cXjtFamsbg%3D 18203325
44. A. Hoque H. Chen X.C. Xu 2008 Statin induces apoptosis and cell growth arrest in prostate cancer cells Cancer Epidemiol. Biomarkers Prev. 17 88 94 10.1158/1055-9965.EPI-07-0531 1:CAS:528:DC%2BD1cXmt12nsg%3D%3D 18199714 (Pubitemid 351196277)
45. K.A. Oliveira K.G. Zecchin L.C. Alberici R.F. Castilho A.E. Vercesi 2008 Simvastatin inducing PC3 prostate cancer cell necrosis mediated by calcineurin and mitochondrial dysfunction J. Bioenerg. Biomembr. 40 307 14 10.1007/s10863-008-9155-9 1:CAS:528:DC%2BD1cXhtlyjsLnM 18679777
46. S. Tavintharan C.N. Ong K. Jeyaseelan M. Sivakumar S.C. Lim C.F. Sum 2007 Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated with high-dose simvastatin: a possible role in statininduced hepatotoxicity? Toxicol. Appl. Pharmacol. 223 173 9 10.1016/j.taap.2007.05.013 1:CAS:528:DC%2BD2sXhtVWit7fL 17610923 (Pubitemid 47348060)
47. I. Kenis S. Tartakover-Matalon N. Cherepnin L. Drucker A. Fishman M. Pomeranz, et al. 2005 Simvastatin has deleterious effects on human first trimester placental explants Hum. Reprod. 20 2866 72 10.1093/humrep/dei120 1:CAS:528:DC%2BD2MXhtVelsLbN 15958395 (Pubitemid 41487645)
48. A.K. Van Vliet P. Nègre-Aminou G.C. van Thiel P.A. Bolhuis L.H. Cohen 1996 Action of lovastatin, simvastatin, and pravastatin on sterol synthesis and their antiproliferative effect in cultured myoblasts from human striated muscle Biochem. Pharmacol. 52 1387 92 10.1016/S0006-2952(96)00467-4 8937448 (Pubitemid 26366362)
49. N. Tomiyama S. Matzno C. Kitada E. Nishiguchi N. Okamura K. Matsuyama 2008 The possibility of simvastatin as a chemotherapeutic agent for all-trans retinoic acid-resistant promyelocytic leukemia Biol. Pharm. Bull. 31 369 74 10.1248/bpb.31.369 1:CAS:528:DC%2BD1cXmtlaksbc%3D 18310894 (Pubitemid 351442129)
50. L.M. Blanco-Colio P. Justo I. Daehn C. Lorz A. Ortiz J. Egido 2003 Bcl-xL overexpression protects from apoptosis induced by HMG-CoA reductase inhibitors in murine tubular cells Kidney Int. 64 181 91 10.1046/j.1523-1755.2003.00080.x 1:CAS:528:DC%2BD3sXlsFeksro%3D 12787408 (Pubitemid 36714170)
51. S. Kaneta K. Satoh S. Kano M. Kanda K. Ichihara 2003 All hydrophobic HMG-CoA reductase inhibitors induce apoptotic death in rat pulmonary vein endothelial cells Atherosclerosis 170 237 43 10.1016/S0021-9150(03)00301-0 1:CAS:528:DC%2BD3sXovVenurY%3D 14612203 (Pubitemid 37377795)
52. P. Kaufmann M. Török A. Zahno K.M. Waldhauser K. Brecht S. Krähenbühl 2006 Toxicity of statins on rat skeletal muscle mitochondria Cell Mol. Life Sci. 63 2415 25 10.1007/s00018-006-6235-z 1:CAS:528:DC%2BD28XhtFyrtrvF 17013560 (Pubitemid 44653050)
53. P. März U. Otten A.R. Miserez 2007 Statins induce differentiation and cell death in neurons and astroglia Glia 55 1 12 10.1002/glia.20422 16998865 (Pubitemid 44845504)
54. G.Q. Xu W.F. Huang H. Liu Y.C. Yang W. Liu 2008 Simvastatin-induced apoptosis of K562 cells is mediated by endoplasmic reticulum stress Yao Xue Xue Bao 43 371 7 1:CAS:528:DC%2BD1cXnt12qs7g%3D 18664198
55. D.S. Park H.S. So J.H. Lee H.Y. Park Y.J. Lee J.H. Cho, et al. 2009 Simvastatin treatment induces morphology alterations and apoptosis in murine cochlear neuronal cells Acta Otolaryngol. 129 166 74 10.1080/00016480802163358 1:CAS:528:DC%2BD1MXotlyntQ%3D%3D 18607908
56. W. Martinet D.M. Schrijvers J.P. Timmermans H. Bult 2008 Interactions between cell death induced by statins and 7-ketocholesterol in rabbit aorta smooth muscle cells Br. J. Pharmacol. 154 1236 46 10.1038/bjp.2008.181 1:CAS:528:DC%2BD1cXosVCjtLs%3D 18469840 (Pubitemid 351992056)
57. O.O. Ogunwobi I.L. Beales 2008 Statins inhibit proliferation and induce apoptosis in Barrett's esophageal adenocarcinoma cells Am. J. Gastroenterol. 103 825 37 10.1111/j.1572-0241.2007.01773.x 1:CAS:528:DC%2BD1cXls1CqsL0%3D 18371146 (Pubitemid 351501115)
58. A. Kettawan T. Takahashi R. Kongkachuichai S. Charoenkiatkul T. Kishi T. Okamoto 2007 Protective effects of coenzyme Q10 on decreased oxidative stress resistance induced by simvastatin J. Clin. Biochem. Nutr. 40 194 202 10.3164/jcbn.40.194 1:CAS:528:DC%2BD2sXovFajs78%3D 18398496 (Pubitemid 46984212)
59. S.A. Glynn D. O'sullivan A.J. Eustace M. Clynes N. O'Donovan 2008 The 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors, simvastatin, lovastatin and mevastatin inhibit proliferation and invasion of melanoma cells BMC Cancer 8 9 10.1186/1471-2407-8-9 18199328 (Pubitemid 351309029)
60. M.F. Demierre P.D. Higgins S.B. Gruber E. Hawk S.M. Lippman 2005 Statins and cancer prevention Nat. Rev. Cancer 5 930 42 10.1038/nrc1751 1:CAS:528:DC%2BD2MXht1ykurbL 16341084 (Pubitemid 41766782)
61. H. Kaji J. Naito Y. Inoue H. Sowa T. Sugimoto K. Chihara 2008 Statin suppresses apoptosis in osteoblastic cells: role of transforming growth factor-beta-Smad3 pathway Horm. Metab. Res. 40 746 51 10.1055/s-0028-1082051 1:CAS:528:DC%2BD1MXlsFWntg%3D%3D 18622892
62. B.A. Schick R. Laaksonen J.J. Frohlich H. Päivä T. Lehtimäki K.H. Humphries, et al. 2007 Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin Clin. Pharmacol. Ther. 81 650 3 10.1038/sj.clpt.6100124 1:CAS:528:DC%2BD2sXlsFCqs7g%3D 17329991 (Pubitemid 46625111)
63. G. DePinieux P. Chariot M. AmmiSaid F. Louarn J.L. Lejonc A. Astier, et al. 1996 Lipid-lowering drugs and mitochondrial function: Effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio Brit. J. Clin. Pharmacol. 42 333 7 10.1046/j.1365-2125.1996.04178.x 1:STN:280:DyaK2s%2FjtFSqug%3D%3D
64. K. Satoh A. Yamato T. Nakai K. Hoshi K. Ichihara 1995 Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in ischaemic dog hearts Br. J. Pharmacol. 116 1894 8 1:CAS:528:DyaK2MXosVaitr8%3D 8528576
65. J.M. Young C.M. Florkowski S.L. Molyneux R.G. McEwan C.M. Frampton P.M. George, et al. 2007 Effect of coenzyme Q(10) supplementation on simvastatin-induced myalgia Am. J. Cardiol. 100 1400 3 10.1016/j.amjcard.2007. 06.030 1:CAS:528:DC%2BD2sXhtF2itLbF 17950797 (Pubitemid 47576018)
66. L. Marcoff P.D. Thompson 2007 The role of coenzyme Q10 in statin-associated myopathy: a systematic review J. Am. Coll. Cardiol. 49 2231 7 10.1016/j.jacc.2007.02.049 1:CAS:528:DC%2BD2sXmtlWisrg%3D 17560286 (Pubitemid 46856819)
67. P. Sirvent S. Bordenave M. Vermaelen B. Roels G. Vassort J. Mercier, et al. 2005 Simvastatin induces impairment in skeletal muscle while heart is protected Biochem. Biophys. Res. Commun 338 1426 34 10.1016/j.bbrc.2005.10.108 1:CAS:528:DC%2BD2MXht1egs7%2FL 16271704 (Pubitemid 41608410)
68. S. Nadanaciva J.A. Dykens A. Bernal R.A. Capaldi Y. Will 2007 Mitochondrial impairment by PPAR agonists and statins identified via immunocaptured OXPHOS complex activities and respiration Toxicol. Appl. Pharmacol. 223 277 87 10.1016/j.taap.2007.06.003 1:CAS:528:DC%2BD2sXhtVWhsbnJ 17658574 (Pubitemid 47362220)
69. J.A. Velho H. Okanobo G.R. Degasperi M.Y. Matsumoto L.C. Alberici R.G. Cosso, et al. 2006 Statins induce calcium-dependent mitochondrial permeability transition Toxicology 219 124 32 10.1016/j.tox.2005.11.007 1:CAS:528: DC%2BD28Xls1emug%3D%3D 16343726 (Pubitemid 43120712)
70. E.S. Alnemri D.J. Livingston D.W. Nicholson G. Salvesen N.A. Thornberry W.W. Wong, et al. 1996 Human ICE/CED-3 protease nomenclature Cell 87 171 10.1016/S0092-8674(00)81334-3 1:CAS:528:DyaK28XmsVGhs7k%3D 8861900
71. R.U. Jänicke M.L. Sprengart M.R. Wati A.G. Porter 1998 Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis J. Biol. Chem. 273 9357 60 10.1074/jbc.273.16.9357 9545256 (Pubitemid 28183012)
72. J.M. Garland C. Rudin 1998 Cytochrome c induces caspase-dependent apoptosis in intact hematopoietic cells and overrides apoptosis suppression mediated by bcl-2, growth factor signaling, MAP-kinase-kinase, and malignant change Blood 92 1235 46 1:CAS:528:DyaK1cXlsVWrsbk%3D 9694712
73. R.M. Kluck E. Bossy-Wetzel D.R. Green D.D. Newmeyer 1997 The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis Science 275 1132 6 10.1126/science.275.5303.1132 1:CAS:528:DyaK2sXhtlKjtro%3D 9027315 (Pubitemid 27097313)
74. X. Liu C.N. Kim J. Yang R. Jemmerson X. Wang 1996 Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c Cell 86 147 57 10.1016/S0092-8674(00)80085-9 1:CAS:528:DyaK28XktlGnsbY%3D 8689682 (Pubitemid 26256586)
75. I. Budihardjo H. Oliver M. Lutter X. Luo X. Wang 1999 Biochemical pathways of caspase activation during apoptosis Annu. Rev. Cell Dev. Biol. 15 269 90 10.1146/annurev.cellbio.15.1.269 1:CAS:528:DC%2BD3cXhtVSnuro%3D 10611963 (Pubitemid 32250377)
76. P. Li D. Nijhawan I. Budihardjo S.M. Srinivasula M. Ahmad E.S. Alnemri X. Wang 1997 Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade Cell 91 479 89 10.1016/S0092-8674(00) 80434-1 1:CAS:528:DyaK2sXnsFGls70%3D 9390557
77. G. Pan K. O'Rourke V.M. Dixit 1998 Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex J. Biol. Chem. 273 5841 5 10.1074/jbc.273.10.5841 1:CAS:528:DyaK1cXhsleitbo%3D 9488720 (Pubitemid 28124061)