Abstract
Statins are widely used and well tolerated cholesterol-lowering drugs, and when used for therapy purposes reduce morbidity and mortality from coronary heart disease. Simvastatin is one of nine known statins, specific inhibitors of hepatic enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase, the rate-limiting step of cholesterol biosynthesis, and is believed to reduce plasma cholesterol levels by decreasing the activity of this enzyme. Statin drugs represent the major improvement in the treatment of hypercholesterolemia that constitutes the main origin of atherosclerosis, leading to coronary heart disease. Although statins are generally safe, minor and severe adverse reactions are well known complications of statin use. Adverse events associated with simvastatin therapy are uncommon, but potentially serious. In this review some details about statins including their adverse effects in humans and animals, the effects of simvastatin on various intracellular and mitochondrial processes, and molecular mechanisms underlying simvastatin cytotoxicity are discussed.
[1] Evans M., Rees A., Effects of HMG-CoA reductase inhibitors on skeletal muscle: are all statins the same? Drug Saf., 2002, 25, 649–663 http://dx.doi.org/10.2165/00002018-200225090-0000410.2165/00002018-200225090-00004Search in Google Scholar PubMed
[2] Kent D.M., Stroke — An Equal Opportunity for the Initiation of Statin Therapy, N. Engl. J. Med., 2006, 355, 613–5 http://dx.doi.org/10.1056/NEJMe06814610.1056/NEJMe068146Search in Google Scholar PubMed
[3] Illingworth D.R., An overview of lipid-lowering drugs, Drugs, 1988, 36Suppl 3, 63–71 http://dx.doi.org/10.2165/00003495-198800363-0001510.2165/00003495-198800363-00015Search in Google Scholar PubMed
[4] Walker J.F., HMG CoA reductase inhibitors, Current clinical experience, Drugs, 1988, 36Suppl 3, 83–6 http://dx.doi.org/10.2165/00003495-198800363-0001710.2165/00003495-198800363-00017Search in Google Scholar PubMed
[5] Qiao Z., Ren J., Chen H., Simvastatin reduces expression and activity of lipoprotein-associated phospholipase A(2) in the aorta of hypercholesterolaemic atherosclerotic rabbits, J. Int. Med. Res., 2009, 37, 1029–37 10.1177/147323000903700407Search in Google Scholar PubMed
[6] Corti R., Osende J.I., Fallon J.T., Fuster V., Mizsei G., Jneid H., et al., 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., 2004, 43, 464–73 http://dx.doi.org/10.1016/j.jacc.2003.08.04810.1016/j.jacc.2003.08.048Search in Google Scholar PubMed
[7] Werner N., Kosiol S., Schiegl T., Ahlers P., Walenta K., Link A., et al., Circulating Endothelial Progenitor Cells and Cardiovascular Outcomes, N. Engl. J. Med., 2005, 353, 999–1007 http://dx.doi.org/10.1056/NEJMoa04381410.1056/NEJMoa043814Search in Google Scholar PubMed
[8] Dirks A.J., Jones K.M., Statin-induced apoptosis and skeletal myopathy, Am. J. Physiol. Cell Physiol., 2006, 291, C1208–12 http://dx.doi.org/10.1152/ajpcell.00226.200610.1152/ajpcell.00226.2006Search in Google Scholar PubMed
[9] Maron D.J., Fazio S., Linton M.F., Current perspectives on statins, Circulation, 2000, 101, 207–13 10.1161/01.CIR.101.2.207Search in Google Scholar
[10] Palinski W., Napoli C., Unraveling pleiotropic effects of statins on plaque rupture, Arterioscler. Thromb. Vasc. Biol., 2002, 22, 1745–50 http://dx.doi.org/10.1161/01.ATV.0000038754.39483.CD10.1161/01.ATV.0000038754.39483.CDSearch in Google Scholar PubMed
[11] Manzoni M., Rollini M., Biosynthesis and biotechnological production of statins by filamentous fungi and application of these cholesterol-lowering drugs, Appl. Microbiol. Biotechnol., 2002, 58, 555–64 http://dx.doi.org/10.1007/s00253-002-0932-910.1007/s00253-002-0932-9Search in Google Scholar PubMed
[12] Schachter M., Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update, Fundam. Clin. Pharmacol., 2005, 19, 117–25 http://dx.doi.org/10.1111/j.1472-8206.2004.00299.x10.1111/j.1472-8206.2004.00299.xSearch in Google Scholar PubMed
[13] Shepherd J., Who should receive a statin these days? Lessons from recent clinical trials, J. Intern. Med., 2006, 260, 305–9 http://dx.doi.org/10.1111/j.1365-2796.2006.01700.x10.1111/j.1365-2796.2006.01700.xSearch in Google Scholar PubMed
[14] Sirvent P., Mercier J., Vassort G., Lacampagne A., Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle, Biochem. Biophys. Res. Commun., 2005, 329, 1067–75 http://dx.doi.org/10.1016/j.bbrc.2005.02.07010.1016/j.bbrc.2005.02.070Search in Google Scholar PubMed
[15] MRC/BHF Heart Protection Study Collaborative Group, Armitage J., Bowman L., Collins R., Parish S., Tobert J., 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. 2009, 9, 6 http://dx.doi.org/10.1186/1471-2210-9-610.1186/1471-2210-9-6Search in Google Scholar PubMed PubMed Central
[16] Goli A.K., Goli S.A., Byrd R.P., Roy T.M., Simvastatin-induced lactic acidosis: a rare adverse reaction? Clin. Pharmacol. Ther., 2002, 72, 461–4 http://dx.doi.org/10.1067/mcp.2002.12794310.1067/mcp.2002.127943Search in Google Scholar PubMed
[17] Thompson P.D., Clarkson P., Karas R.H., Statin-associated myopathy, JAMA, 2003, 289, 1681–90 http://dx.doi.org/10.1001/jama.289.13.168110.1001/jama.289.13.1681Search in Google Scholar PubMed
[18] Venero C.V., Thompson P.D., Managing statin myopathy, Endocrinol. Metab. Clin. North. Am., 2009, 38, 121–36 http://dx.doi.org/10.1016/j.ecl.2008.11.00210.1016/j.ecl.2008.11.002Search in Google Scholar PubMed
[19] Omar M.A., Wilson J.P., FDA adverse event reports on statin-associated rhabdomyolysis, Ann. Pharmacother., 2002, 36, 288–95 http://dx.doi.org/10.1345/aph.1A28910.1345/aph.1A289Search in Google Scholar PubMed
[20] Staffa J.A., Chang J., Green L., Cerivastatin and reports of fatal rhabdomyolysis, N. Engl. J. Med., 2002, 346, 539–40 http://dx.doi.org/10.1056/NEJM20020214346072110.1056/NEJM200202143460721Search in Google Scholar PubMed
[21] Ballarè M., Campanini M., Airoldi G., Zaccala G., Bertoncelli M.C., Cornaglia G., et al., Hepatotoxicity of hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors, Minerva Gastroenterol. Dietol., 1992, 38, 41–4 Search in Google Scholar
[22] Waness A., Bahlas S., Al Shohaib S., Simvastatin-induced rhabdomyolysis and acute renal injury, Blood Purif., 2008, 26, 394–8 http://dx.doi.org/10.1159/00014193110.1159/000141931Search in Google Scholar PubMed
[23] Qari F.A., Severe rhabdomyolysis and acute renal failure secondary to use of simvastatin in undiagnosed hypothyroidism, Saudi J. Kidney Dis. Transpl., 2009, 20, 127–9 Search in Google Scholar
[24] Marie I, Delafenêtre H, Massy N, Thuillez C, Noblet C; Network of the French Pharmacovigilance Centers, Tendinous disorders attributed to statins: a study on ninety-six spontaneous reports in the period 1990–2005 and review of the literature, Arthritis Rheum., 2008, 59, 367–72 http://dx.doi.org/10.1002/art.2330910.1002/art.23309Search in Google Scholar PubMed
[25] Bae J., Jarcho J.A., Denton M.D., Magee C.C., Statin specific toxicity in organ transplant recipients: case report and review of the literature, J. Nephrol., 2002, 15, 317–9 Search in Google Scholar
[26] Evangelista T., Ferro J., Pereira P., de Carvalho M., A case of asymptomatic cytoplasmic body myopathy revealed by sinvastatin, Neuromuscul. Disord., 2009, 19, 66–8 http://dx.doi.org/10.1016/j.nmd.2008.10.00810.1016/j.nmd.2008.10.008Search in Google Scholar PubMed
[27] Tuteja S., Pyrsopoulos N.T., Wolowich W.R., Khanmoradi K., Levi D.M., Selvaggi G., et al., Simvastatin-ezetimibe-induced hepatic failure necessitating liver transplantation, Pharmacotherapy, 2008, 28, 1188–93 http://dx.doi.org/10.1592/phco.28.9.118810.1592/phco.28.9.1188Search in Google Scholar PubMed
[28] Kanathur N., Mathai M.G., Byrd R.P., Fields C.L., Roy T.M., Simvastatin-diltiazem drug interaction resulting in rhabdomyolysis and hepatitis, Tenn. Med., 2001, 94, 339–41 Search in Google Scholar
[29] Johnson J.L., Loomis I.B., A case of simvastatin-associated pancreatitis and review of statin-associated pancreatitis, Pharmacotherapy, 2006, 26, 414–22 http://dx.doi.org/10.1592/phco.26.3.41410.1592/phco.26.3.414Search in Google Scholar PubMed
[30] Singh S., Loke Y.K., Statins and pancreatitis: a systematic review of observational studies and spontaneous case reports, Drug Saf., 2006, 29, 1123–32 http://dx.doi.org/10.2165/00002018-200629120-0000410.2165/00002018-200629120-00004Search in Google Scholar PubMed
[31] Bielecki J.W., Schraner C., Briner V., Kuhn M., Rhabdomyolysis and cholestatic hepatitis under treatment with simvastatin and chlorzoxazone, Schweiz. Med. Wochenschr., 1999, 129, 514–8 Search in Google Scholar
[32] Rifkin S.I., Multiple drug interactions in a renal transplant patient leading to simvastatin-induced rhabdomyolysis: a case report, Medscape J. Med., 2008, 10, 264 Search in Google Scholar
[33] Francis L., Bonilla E., Soforo E., Neupane H., Nakhla H., Fuller C., et al.. Fatal toxic myopathy attributed to propofol, methylprednisolone, and cyclosporine after prior exposure to colchicine and simvastatin, Clin. Rheumatol., 2008, 27, 129–31 http://dx.doi.org/10.1007/s10067-007-0696-910.1007/s10067-007-0696-9Search in Google Scholar PubMed
[34] Nakahara K., Kuriyama M., Sonoda Y., Yoshidome H., Nakagawa H., Fujiyama J., et al., Myopathy induced by HMG-CoA reductase inhibitors in rabbits: a pathological, electrophysiological, and biochemical study, Toxicol. Appl. Pharmacol., 1998, 152, 99–106 http://dx.doi.org/10.1006/taap.1998.849110.1006/taap.1998.8491Search in Google Scholar PubMed
[35] Westwood F.R., Bigley A., Randall K., Marsden A.M., Scott R.C., Statin-induced muscle necrosis in the rat: distribution, development, and fibre selectivity, Toxicol. Pathol. 2005, 33, 246–57 http://dx.doi.org/10.1080/0192623059090821310.1080/01926230590908213Search in Google Scholar PubMed
[36] Baytan S.H., Alkanat M., Okuyan M., Ekinci M., Gedikli E., Ozeren M., Simvastatin impairs spatial memory in rats at a specific dose level, Tohoku J. Exp. Med., 2008, 214, 341–9 http://dx.doi.org/10.1620/tjem.214.34110.1620/tjem.214.341Search in Google Scholar PubMed
[37] Oms P., Assie N., Bruniquel F., Degryse A.D., van Haverbeke G., Delhon A., 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., 1995, 77, 391–6 http://dx.doi.org/10.1111/j.1600-0773.1995.tb01048.x10.1111/j.1600-0773.1995.tb01048.xSearch in Google Scholar
[38] Cenedella R.J., Neely A.R., Sexton P., Concentration and distribution of ubiquinone (coenzyme Q), the endogenous lipid antioxidant, in the rat lens: effect of treatment with simvastatin, Mol. Vis., 2005, 11, 594–602 Search in Google Scholar
[39] Sacher J., Weigl L., Werner M., Szegedi C., Hohenegger M., Delineation of myotoxicity induced by 3-hydroxy-3-methylglutaryl CoA reductase inhibitors in human skeletal muscle cells, J. Pharmac. Exp. Ther., 2005, 314, 1032–41 http://dx.doi.org/10.1124/jpet.105.08646210.1124/jpet.105.086462Search in Google Scholar
[40] Demyanets S., Kaun C., Pfaffenberger S., Hohensinner P.J., Rega G., Pammer J., et al., Hydroxymethylglutaryl-coenzyme A reductase inhibitors induce apoptosis in human cardiac myocytes in vitro, Biochem. Pharmacol., 2006, 71, 1324–30 http://dx.doi.org/10.1016/j.bcp.2006.01.01610.1016/j.bcp.2006.01.016Search in Google Scholar
[41] Cafforio P., Dammacco F., Gernone A., Silvestris F., Statins activate the mitochondrial pathway of apoptosis in human lymphoblasts and myeloma cells, Carcinogenesis, 2005, 26, 883–91 http://dx.doi.org/10.1093/carcin/bgi03610.1093/carcin/bgi036Search in Google Scholar
[42] Boucher K., Siegel C.S., Sharma P., Hauschka P.V., Solomon K.R., HMG-CoA reductase inhibitors induce apoptosis in pericytes, Microvasc. Res., 2006, 71, 91–102 http://dx.doi.org/10.1016/j.mvr.2005.11.00710.1016/j.mvr.2005.11.007Search in Google Scholar
[43] Yokota K., Miyoshi F., Miyazaki T., Sato K., Yoshida Y., Asanuma Y., et al., High concentration simvastatin induces apoptosis in fibroblast-like synoviocytes from patients with rheumatoid arthritis, J. Rheumatol., 2008, 35, 193–200 Search in Google Scholar
[44] Hoque A., Chen H., Xu X.C., Statin induces apoptosis and cell growth arrest in prostate cancer cells, Cancer Epidemiol. Biomarkers Prev., 2008, 17, 88–94 http://dx.doi.org/10.1158/1055-9965.EPI-07-053110.1158/1055-9965.EPI-07-0531Search in Google Scholar
[45] Oliveira K.A., Zecchin K.G., Alberici L.C., Castilho R.F., Vercesi A.E., Simvastatin inducing PC3 prostate cancer cell necrosis mediated by calcineurin and mitochondrial dysfunction, J. Bioenerg. Biomembr., 2008, 40, 307–14 http://dx.doi.org/10.1007/s10863-008-9155-910.1007/s10863-008-9155-9Search in Google Scholar
[46] Tavintharan S., Ong C.N., Jeyaseelan K., Sivakumar M., Lim S.C., Sum C.F., Reduced mitochondrial coenzyme Q10 levels in HepG2 cells treated with high-dose simvastatin: a possible role in statininduced hepatotoxicity? Toxicol. Appl. Pharmacol., 2007, 223, 173–9 http://dx.doi.org/10.1016/j.taap.2007.05.01310.1016/j.taap.2007.05.013Search in Google Scholar
[47] Kenis I., Tartakover-Matalon S., Cherepnin N., Drucker L., Fishman A., Pomeranz M., et al., Simvastatin has deleterious effects on human first trimester placental explants, Hum. Reprod., 2005, 20, 2866–72 http://dx.doi.org/10.1093/humrep/dei12010.1093/humrep/dei120Search in Google Scholar
[48] Van Vliet A.K., Nègre-Aminou P., van Thiel G.C., Bolhuis P.A., Cohen L.H., Action of lovastatin, simvastatin, and pravastatin on sterol synthesis and their antiproliferative effect in cultured myoblasts from human striated muscle, Biochem. Pharmacol., 1996, 52, 1387–92 http://dx.doi.org/10.1016/S0006-2952(96)00467-410.1016/S0006-2952(96)00467-4Search in Google Scholar
[49] Tomiyama N., Matzno S., Kitada C., Nishiguchi E., Okamura N., Matsuyama K., The possibility of simvastatin as a chemotherapeutic agent for all-trans retinoic acid-resistant promyelocytic leukemia, Biol. Pharm. Bull., 2008, 31, 369–74 http://dx.doi.org/10.1248/bpb.31.36910.1248/bpb.31.369Search in Google Scholar
[50] Blanco-Colio L.M., Justo P., Daehn I., Lorz C., Ortiz A., Egido J., Bcl-xL overexpression protects from apoptosis induced by HMG-CoA reductase inhibitors in murine tubular cells, Kidney Int., 2003, 64, 181–91 http://dx.doi.org/10.1046/j.1523-1755.2003.00080.x10.1046/j.1523-1755.2003.00080.xSearch in Google Scholar
[51] Kaneta S., Satoh K., Kano S., Kanda M., Ichihara K., All hydrophobic HMG-CoA reductase inhibitors induce apoptotic death in rat pulmonary vein endothelial cells, Atherosclerosis, 2003, 170, 237–43 http://dx.doi.org/10.1016/S0021-9150(03)00301-010.1016/S0021-9150(03)00301-0Search in Google Scholar
[52] Kaufmann P., Török M., Zahno A., Waldhauser K.M., Brecht K., Krähenbühl S., Toxicity of statins on rat skeletal muscle mitochondria, Cell Mol. Life Sci., 2006, 63, 2415–25 http://dx.doi.org/10.1007/s00018-006-6235-z10.1007/s00018-006-6235-zSearch in Google Scholar PubMed
[53] März P., Otten U., Miserez A.R., Statins induce differentiation and cell death in neurons and astroglia, Glia, 2007, 55, 1–12 http://dx.doi.org/10.1002/glia.2042210.1002/glia.20422Search in Google Scholar PubMed
[54] Xu G.Q., Huang W.F., Liu H., Yang Y.C., Liu W., Simvastatin-induced apoptosis of K562 cells is mediated by endoplasmic reticulum stress, Yao Xue Xue Bao, 2008, 43, 371–7 Search in Google Scholar
[55] Park D.S., So H.S., Lee J.H., Park H.Y., Lee Y.J., Cho J.H., et al., Simvastatin treatment induces morphology alterations and apoptosis in murine cochlear neuronal cells, Acta Otolaryngol., 2009, 129, 166–74 http://dx.doi.org/10.1080/0001648080216335810.1080/00016480802163358Search in Google Scholar PubMed
[56] Martinet W., Schrijvers D.M., Timmermans J.P., Bult H., Interactions between cell death induced by statins and 7-ketocholesterol in rabbit aorta smooth muscle cells, Br. J. Pharmacol., 2008, 154, 1236–46 http://dx.doi.org/10.1038/bjp.2008.18110.1038/bjp.2008.181Search in Google Scholar PubMed PubMed Central
[57] Ogunwobi O.O., Beales I.L., Statins inhibit proliferation and induce apoptosis in Barrett’s esophageal adenocarcinoma cells, Am. J. Gastroenterol., 2008, 103, 825–37 http://dx.doi.org/10.1111/j.1572-0241.2007.01773.x10.1111/j.1572-0241.2007.01773.xSearch in Google Scholar PubMed
[58] Kettawan A., Takahashi T., Kongkachuichai R., Charoenkiatkul S., Kishi T., Okamoto T., Protective effects of coenzyme Q10 on decreased oxidative stress resistance induced by simvastatin, J. Clin. Biochem. Nutr., 2007, 40, 194–202 http://dx.doi.org/10.3164/jcbn.40.19410.3164/jcbn.40.194Search in Google Scholar PubMed PubMed Central
[59] Glynn S.A., O’sullivan D., Eustace A.J., Clynes M., O’Donovan N., The 3-hydroxy-3-methylglutarylcoenzyme A reductase inhibitors, simvastatin, lovastatin and mevastatin inhibit proliferation and invasion of melanoma cells, BMC Cancer, 2008, 8, 9 http://dx.doi.org/10.1186/1471-2407-8-910.1186/1471-2407-8-9Search in Google Scholar PubMed PubMed Central
[60] Demierre M.F., Higgins P.D., Gruber S.B., Hawk E., Lippman S.M., Statins and cancer prevention, Nat. Rev. Cancer, 2005, 5, 930–42 http://dx.doi.org/10.1038/nrc175110.1038/nrc1751Search in Google Scholar PubMed
[61] Kaji H., Naito J., Inoue Y., Sowa H., Sugimoto T., Chihara K., Statin suppresses apoptosis in osteoblastic cells: role of transforming growth factor-beta-Smad3 pathway, Horm. Metab. Res., 2008, 40, 746–51 http://dx.doi.org/10.1055/s-0028-108205110.1055/s-0028-1082051Search in Google Scholar PubMed
[62] Schick B.A., Laaksonen R., Frohlich J.J., Päivä H., Lehtimäki T., Humphries K.H., et al., Decreased skeletal muscle mitochondrial DNA in patients treated with high-dose simvastatin, Clin. Pharmacol. Ther., 2007, 81, 650–3 http://dx.doi.org/10.1038/sj.clpt.610012410.1038/sj.clpt.6100124Search in Google Scholar PubMed
[63] DePinieux G., Chariot P., AmmiSaid M., Louarn F., Lejonc J.L., Astier A., et al., Lipid-lowering drugs and mitochondrial function: Effects of HMG-CoA reductase inhibitors on serum ubiquinone and blood lactate/pyruvate ratio, Brit. J. Clin. Pharmacol., 1996, 42, 333–7 http://dx.doi.org/10.1046/j.1365-2125.1996.04178.x10.1046/j.1365-2125.1996.04178.xSearch in Google Scholar PubMed PubMed Central
[64] Satoh K., Yamato A., Nakai T., Hoshi K., Ichihara K., Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on mitochondrial respiration in ischaemic dog hearts, Br. J. Pharmacol., 1995, 116, 1894–8 10.1111/j.1476-5381.1995.tb16679.xSearch in Google Scholar PubMed PubMed Central
[65] Young J.M., Florkowski C.M., Molyneux S.L., McEwan R.G., Frampton C.M., George P.M., et al., Effect of coenzyme Q(10) supplementation on simvastatin-induced myalgia, Am. J. Cardiol., 2007, 100, 1400–3 http://dx.doi.org/10.1016/j.amjcard.2007.06.03010.1016/j.amjcard.2007.06.030Search in Google Scholar PubMed
[66] Marcoff L., Thompson P.D., The role of coenzyme Q10 in statin-associated myopathy: a systematic review, J. Am. Coll. Cardiol., 2007, 49, 2231–7 http://dx.doi.org/10.1016/j.jacc.2007.02.04910.1016/j.jacc.2007.02.049Search in Google Scholar PubMed
[67] Sirvent P., Bordenave S., Vermaelen M., Roels B., Vassort G., Mercier J., et al., Simvastatin induces impairment in skeletal muscle while heart is protected, Biochem. Biophys. Res. Commun, 2005, 338, 1426–34 http://dx.doi.org/10.1016/j.bbrc.2005.10.10810.1016/j.bbrc.2005.10.108Search in Google Scholar PubMed
[68] Nadanaciva S., Dykens J.A., Bernal A., Capaldi R.A., Will Y., Mitochondrial impairment by PPAR agonists and statins identified via immunocaptured OXPHOS complex activities and respiration, Toxicol. Appl. Pharmacol., 2007, 223, 277–87 http://dx.doi.org/10.1016/j.taap.2007.06.00310.1016/j.taap.2007.06.003Search in Google Scholar PubMed
[69] Velho J.A., Okanobo H., Degasperi G.R., Matsumoto M.Y., Alberici L.C., Cosso R.G., et al., Statins induce calcium-dependent mitochondrial permeability transition, Toxicology, 2006, 219, 124–32 http://dx.doi.org/10.1016/j.tox.2005.11.00710.1016/j.tox.2005.11.007Search in Google Scholar PubMed
[70] Alnemri E.S., Livingston D.J., Nicholson D.W., Salvesen G., Thornberry N.A., Wong W.W., et al., Human ICE/CED-3 protease nomenclature, Cell, 1996, 87, 171 http://dx.doi.org/10.1016/S0092-8674(00)81334-310.1016/S0092-8674(00)81334-3Search in Google Scholar
[71] Jänicke R.U., Sprengart M.L., Wati M.R., Porter A.G., Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis, J. Biol. Chem., 1998, 273, 9357–60 http://dx.doi.org/10.1074/jbc.273.16.935710.1074/jbc.273.16.9357Search in Google Scholar
[72] Garland J.M., Rudin C., 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, 1998, 92, 1235–46 10.1182/blood.V92.4.1235Search in Google Scholar
[73] Kluck R.M., Bossy-Wetzel E., Green D.R., Newmeyer D.D., The release of cytochrome c from mitochondria: a primary site for Bcl-2 regulation of apoptosis, Science, 1997, 275, 1132–6 http://dx.doi.org/10.1126/science.275.5303.113210.1126/science.275.5303.1132Search in Google Scholar
[74] Liu X., Kim C.N., Yang J., Jemmerson R., Wang X., Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c, Cell, 1996, 86, 147–57 http://dx.doi.org/10.1016/S0092-8674(00)80085-910.1016/S0092-8674(00)80085-9Search in Google Scholar
[75] Budihardjo I., Oliver H., Lutter M., Luo X., Wang X., Biochemical pathways of caspase activation during apoptosis, Annu. Rev. Cell Dev. Biol., 1999, 15, 269–90 http://dx.doi.org/10.1146/annurev.cellbio.15.1.26910.1146/annurev.cellbio.15.1.269Search in Google Scholar
[76] Li P., Nijhawan D., Budihardjo I., Srinivasula S.M., Ahmad M., Alnemri E.S., Wang X., Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade, Cell, 1997, 91, 479–89 http://dx.doi.org/10.1016/S0092-8674(00)80434-110.1016/S0092-8674(00)80434-1Search in Google Scholar
[77] Pan G., O’Rourke K., Dixit V.M., Caspase-9, Bcl-XL, and Apaf-1 form a ternary complex, J. Biol. Chem., 1998, 273, 5841–5 http://dx.doi.org/10.1074/jbc.273.10.584110.1074/jbc.273.10.5841Search in Google Scholar PubMed
© 2010 Versita Warsaw
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.