{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T06:24:07Z","timestamp":1777530247267,"version":"3.51.4"},"reference-count":30,"publisher":"Japanese Pharmacological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Pharmacol Sci"],"published-print":{"date-parts":[[2013]]},"DOI":"10.1254\/jphs.13r06cp","type":"journal-article","created":{"date-parts":[[2013,11,19]],"date-time":"2013-11-19T03:44:13Z","timestamp":1384832653000},"page":"289-294","source":"Crossref","is-referenced-by-count":69,"title":["Mechanism of Statin-Induced Rhabdomyolysis"],"prefix":"10.1254","volume":"123","author":[{"given":"Kazuho","family":"Sakamoto","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junko","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"332","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1 Goldstein JL, Brown MS. The LDL receptor. Arterioscler Thromb Vasc Biol. 2009;29:431\u2013438.","DOI":"10.1161\/ATVBAHA.108.179564"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2 Chin DJ, Gil G, Russell DW, Liscum L, Luskey KL, Basu SK, et al. Nucleotide sequence of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, a glycoprotein of endoplasmic reticulum. Nature. 1984;308:613\u2013617.","DOI":"10.1038\/308613a0"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3 LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a meta-analysis of randomized controlled trials. JAMA. 1999;282:2340\u20132346.","DOI":"10.1001\/jama.282.24.2340"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4 Ballantyne CM, Corsini A, Davidson MH, Holdaas H, Jacobson TA, Leitersdorf E, et al. Risk for myopathy with statin therapy in high-risk patients. Arch Intern Med. 2003;163:553\u2013564.","DOI":"10.1001\/archinte.163.5.553"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5 Westwood FR, Bigley A, Randall K, Marsden AM, Scott RC. Statin-induced muscle necrosis in the rat: distribution, development, and fibre selectivity. Toxicol Pathol. 2005;33:246\u2013257.","DOI":"10.1080\/01926230590908213"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6 Yamamoto A, Sudo H, Endo A. Therapeutic effects of ML-236B in primary hypercholesterolemia. Atherosclerosis. 1980;35:259\u2013266.","DOI":"10.1016\/0021-9150(80)90124-0"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7 Staffa JA, Chang J, Green L. Cerivastatin and reports of fatal rhabdomyolysis. N Engl J Med. 2002;346:539\u2013540.","DOI":"10.1056\/NEJM200202143460721"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8 Shitara Y, Sugiyama Y. Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: drug-drug interactions and interindividual differences in transporter and metabolic enzyme functions. Pharmacol Ther. 2006;112:71\u2013105.","DOI":"10.1016\/j.pharmthera.2006.03.003"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9 Yaffe D. Retention of differentiation potentialities during prolonged cultivation of myogenic cells. Proc Natl Acad Sci U S A. 1968;61:477\u2013483.","DOI":"10.1073\/pnas.61.2.477"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10 Dirks AJ, Jones KM. Statin-induced apoptosis and skeletal myopathy. Am J Physiol Cell Physiol. 2006;291:C1208\u2013C1212.","DOI":"10.1152\/ajpcell.00226.2006"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11 Sakamoto K, Mikami H, Kimura J. Involvement of organic anion transporting polypeptides in the toxicity of hydrophilic pravastatin and lipophilic fluvastatin in rat skeletal myofibres. Br J Pharmacol. 2008;154:1482\u20131490.","DOI":"10.1038\/bjp.2008.192"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12 Itagaki M, Takaguri A, Kano S, Kaneta S, Ichihara K, Satoh K. Possible mechanisms underlying statin-induced skeletal muscle toxicity in L6 fibroblasts and in rats. J Pharmacol Sci. 2009;109:94\u2013101.","DOI":"10.1254\/jphs.08238FP"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13 Masters BA, Palmoski MJ, Flint OP, Gregg RE, Wang-Iverson D, Durham SK. In vitro myotoxicity of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, pravastatin, lovastatin, and simvastatin, using neonatal rat skeletal myocytes. Toxicol Appl Pharmacol. 1995;131:163\u2013174.","DOI":"10.1006\/taap.1995.1058"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14 Bekoff A, Betz WJ. Physiological properties of dissociated muscle fibres obtained from innervated and denervated adult rat muscle. J Physiol. 1977;271:25\u201340.","DOI":"10.1113\/jphysiol.1977.sp011988"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15 Sakamoto K, Honda T, Yokoya S, Waguri S, Kimura J. Rab-small GTPases are involved in fluvastatin and pravastatin-induced vacuolation in rat skeletal myofibers. FASEB J. 2007;21:4087\u20134094.","DOI":"10.1096\/fj.07-8713com"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16 Tanaka S, Sakamoto K, Yamamoto M, Mizuno A, Ono T, Waguri S, et al. Mechanism of statin-induced contractile dysfunction in rat cultured skeletal myofibers. J Pharmacol Sci. 2010;114:454\u2013463.","DOI":"10.1254\/jphs.10229FP"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17 Sakamoto K, Wada I, Kimura J. Inhibition of Rab1 GTPase and endoplasmic reticulum-to-Golgi trafficking underlies statin\u2019s toxicity in rat skeletal myofibers. J Pharmacol Exp Ther. 2011;338:62\u201369.","DOI":"10.1124\/jpet.111.179762"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18 Thompson PD, Zmuda JM, Domalik LJ, Zimet RJ, Staggers J, Guyton JR. Lovastatin increases exercise-induced skeletal muscle injury. Metabolism. 1997;46:1206\u20131210.","DOI":"10.1016\/S0026-0495(97)90218-3"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19 Knauer MJ, Urquhart BL, Meyer zu Schwabedissen HE, Schwarz UI, Lemke CJ, Leake BF, et al. Human skeletal muscle drug transporters determine local exposure and toxicity of statins. Circ Res. 2010;106:297\u2013306.","DOI":"10.1161\/CIRCRESAHA.109.203596"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20 Lane KT, Beese LS. Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. J Lipid Res. 2006;47:681\u2013699.","DOI":"10.1194\/jlr.R600002-JLR200"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21 Flint OP, Masters BA, Gregg RE, Durham SK. Inhibition of cholesterol synthesis by squalene synthase inhibitors does not induce myotoxicity in vitro. Toxicol Appl Pharmacol. 1997;145:91\u201398.","DOI":"10.1006\/taap.1997.8131"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22 Matzno S, Yasuda S, Juman S, Yamamoto Y, Nagareya-Ishida N, Tazuya-Murayama K, et al. Statin-induced apoptosis linked with membrane farnesylated Ras small G protein depletion, rather than geranylated Rho protein. J Pharm Pharmacol. 2005;57:1475\u20131484.","DOI":"10.1211\/jpp.57.11.0014"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23 Cao P, Hanai J, Tanksale P, Imamura S, Sukhatme VP, Lecker SH. Statin-induced muscle damage and atrogin-1 induction is the result of a geranylgeranylation defect. FASEB J. 2009;23:2844\u20132854.","DOI":"10.1096\/fj.08-128843"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24 Bobak D, Moorman J, Guanzon A, Gilmer L, Hahn C. Inactivation of the small GTPase Rho disrupts cellular attachment and induces adhesion-dependent and adhesion-independent apoptosis. Oncogene. 1997;15:2179\u20132189.","DOI":"10.1038\/sj.onc.1201396"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25 Stenmark H. Rab GTPases as coordinators of vesicle traffic. Nat Rev Mol Cell Biol. 2009;10:513\u2013525.","DOI":"10.1038\/nrm2728"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26 Ostrowski SM, Wilkinson BL, Golde TE, Landreth G. Statins reduce amyloid-beta production through inhibition of protein isoprenylation. J Biol Chem. 2007;282:26832\u201326844.","DOI":"10.1074\/jbc.M702640200"},{"key":"27","doi-asserted-by":"crossref","unstructured":"27 Citterio C, Vichi A, Pacheco-Rodriguez G, Aponte AM, Moss J, Vaughan M. Unfolded protein response and cell death after depletion of brefeldin A-inhibited guanine nucleotide-exchange protein GBF1. Proc Natl Acad Sci U S A. 2008;105:2877\u20132882.","DOI":"10.1073\/pnas.0712224105"},{"key":"28","unstructured":"28 Hanai J, Cao P, Tanksale P, Imamura S, Koshimizu E, Zhao J, et al. The muscle-specific ubiquitin ligase atrogin-1\/MAFbx mediates statin-induced muscle toxicity. J Clin Invest. 2007;117:3940\u20133951."},{"key":"29","doi-asserted-by":"crossref","unstructured":"29 Lemasters JJ, Nieminen AL, Qian T, Trost LC, Elmore SP, Nishimura Y, et al. The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta. 1998;1366:177\u2013196.","DOI":"10.1016\/S0005-2728(98)00112-1"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30 Wagner BK, Gilbert TJ, Hanai J, Imamura S, Bodycombe NE, Bon RS, et al. A small-molecule screening strategy to identify suppressors of statin myopathy. ACS Chem Biol. 2011;6:900\u2013904.","DOI":"10.1021\/cb200206w"}],"container-title":["Journal of Pharmacological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jphs\/123\/4\/123_13R06CP\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T15:11:15Z","timestamp":1621437075000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/jphs\/123\/4\/123_13R06CP\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013]]},"references-count":30,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013]]}},"URL":"https:\/\/doi.org\/10.1254\/jphs.13r06cp","relation":{},"ISSN":["1347-8613","1347-8648"],"issn-type":[{"value":"1347-8613","type":"print"},{"value":"1347-8648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013]]}}}