PL EN


Preferencje help
Widoczny [Schowaj] Abstrakt
Liczba wyników
Czasopismo
2010 | 5 | 3 | 269-279
Tytuł artykułu

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

Treść / Zawartość
Warianty tytułu
Języki publikacji
EN
Abstrakty
EN
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.
Słowa kluczowe
Wydawca
Czasopismo
Rocznik
Tom
5
Numer
3
Strony
269-279
Opis fizyczny
Daty
wydano
2010-06-01
online
2010-04-09
Twórcy
  • Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Russia , kaminsky@iteb.ru
  • Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Russia
Bibliografia
  • [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/10.2165/00002018-200225090-00004[Crossref]
  • [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/NEJMe068146[Crossref]
  • [3] Illingworth D.R., An overview of lipid-lowering drugs, Drugs, 1988, 36Suppl 3, 63–71 http://dx.doi.org/10.2165/00003495-198800363-00015[Crossref]
  • [4] Walker J.F., HMG CoA reductase inhibitors, Current clinical experience, Drugs, 1988, 36Suppl 3, 83–6 http://dx.doi.org/10.2165/00003495-198800363-00017[Crossref]
  • [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 [Crossref]
  • [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.2003.08.048[Crossref]
  • [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/NEJMoa043814[Crossref]
  • [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.00226.2006[Crossref]
  • [9] Maron D.J., Fazio S., Linton M.F., Current perspectives on statins, Circulation, 2000, 101, 207–13 [Crossref]
  • [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.CD[Crossref]
  • [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/s00253-002-0932-9[Crossref]
  • [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.x[Crossref]
  • [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.x[Crossref]
  • [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.2005.02.070[Crossref]
  • [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/10.1186/1471-2210-9-6[Crossref]
  • [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.2002.127943[Crossref]
  • [17] Thompson P.D., Clarkson P., Karas R.H., Statin-associated myopathy, JAMA, 2003, 289, 1681–90 http://dx.doi.org/10.1001/jama.289.13.1681[Crossref]
  • [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.2008.11.002[Crossref]
  • [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.1A289[Crossref]
  • [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/NEJM200202143460721[Crossref]
  • [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
  • [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/10.1159/000141931[Crossref]
  • [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
  • [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.23309[Crossref]
  • [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
  • [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.2008.10.008[Crossref]
  • [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.28.9.1188[Crossref]
  • [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
  • [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.26.3.414[Crossref]
  • [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/10.2165/00002018-200629120-00004[Crossref]
  • [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
  • [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
  • [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/s10067-007-0696-9[Crossref]
  • [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.1998.8491[Crossref]
  • [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/10.1080/01926230590908213[Crossref]
  • [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.214.341[Crossref]
  • [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.x[Crossref]
  • [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
  • [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.105.086462[Crossref]
  • [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.2006.01.016[Crossref]
  • [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/bgi036[Crossref]
  • [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.2005.11.007[Crossref]
  • [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
  • [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-07-0531[Crossref]
  • [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/s10863-008-9155-9[Crossref]
  • [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.2007.05.013[Crossref]
  • [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/dei120[Crossref]
  • [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)00467-4[Crossref]
  • [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.31.369[Crossref]
  • [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.x[Crossref]
  • [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)00301-0[Crossref]
  • [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-z[Crossref]
  • [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.20422[Crossref]
  • [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
  • [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/10.1080/00016480802163358[Crossref]
  • [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.2008.181[Crossref]
  • [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.x[Crossref]
  • [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.40.194[Crossref]
  • [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/10.1186/1471-2407-8-9[Crossref]
  • [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/nrc1751[Crossref]
  • [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-0028-1082051[Crossref]
  • [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.6100124[Crossref]
  • [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.x[Crossref]
  • [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
  • [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.2007.06.030[Crossref]
  • [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.2007.02.049[Crossref]
  • [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.2005.10.108[Crossref]
  • [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.2007.06.003[Crossref]
  • [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.2005.11.007[Crossref]
  • [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)81334-3[Crossref]
  • [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.273.16.9357[Crossref]
  • [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
  • [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.275.5303.1132[Crossref]
  • [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)80085-9[Crossref]
  • [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.15.1.269[Crossref]
  • [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)80434-1[Crossref]
  • [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.273.10.5841
Typ dokumentu
Bibliografia
Identyfikatory
Identyfikator YADDA
bwmeta1.element.-psjd-doi-10_2478_s11536-009-0123-5
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.