The AKT/mTOR signaling pathway plays a key role in statin-induced myotoxicity

Biochimica et Biophysica Acta - Molecular Cell Research

Volumn 1853, Issue 8, 2015, Pages 1841-1849

  Bonifacio, Annalisa ^a,b   Sanvee, Gerda M ^a,b   Bouitbir, Jamal ^a,b   Krähenbühl, Stephan ^a,b  

^a UNIVERSITY HOSPITAL BASEL   (Switzerland)

^b UNIVERSITY OF BASEL   (Switzerland)

Author keywords

AKT mTOR signaling pathway; Apoptosis; Atorvastatin; Muscle atrophy; Rosuvastatin; Simvastatin

Indexed keywords

ATORVASTATIN; CASPASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; INITIATION FACTOR 4E BINDING PROTEIN 1; MAMMALIAN TARGET OF RAPAMYCIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PROTEIN KINASE B; PROTEIN S6; ROSUVASTATIN; S6 KINASE; SIMVASTATIN; TRANSCRIPTION FACTOR FKHRL1; MTOR PROTEIN, HUMAN; TARGET OF RAPAMYCIN KINASE;

ANIMAL EXPERIMENT; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CELL STRUCTURE; CONTROLLED STUDY; CYTOTOXICITY; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; MOUSE; MUSCLE ATROPHY; MUSCLE CELL; MUSCLE DISEASE; MYOTOXICITY; MYOTUBE; NONHUMAN; PRIORITY JOURNAL; PROTEIN SYNTHESIS; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; ANIMAL; C57BL MOUSE; CELL CULTURE; CHEMICALLY INDUCED; DRUG EFFECTS; MALE; METABOLISM; PATHOLOGY; PHYSIOLOGY;

MUS;

ANIMALS; APOPTOSIS; CELLS, CULTURED; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MALE; MICE; MICE, INBRED C57BL; MUSCLE FIBERS, SKELETAL; MUSCLE, SKELETAL; MUSCULAR DISEASES; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; SIMVASTATIN; TOR SERINE-THREONINE KINASES;

EID: 84929169969     PISSN: 01674889     EISSN: 18792596     Source Type: Journal    
DOI: 10.1016/j.bbamcr.2015.04.010     Document Type: Article

References (46)

1. Joy T.R., Hegele R.A. Narrative review: statin-related myopathy. Ann. Intern. Med. 2009, 150:858-868.
2. Law M., Rudnicka A.R. Statin safety: a systematic review. Am. J. Cardiol. 2006, 97:52C-60C.
3. Baker S.K. Molecular clues into the pathogenesis of statin-mediated muscle toxicity. Muscle Nerve 2005, 31:572-580.
4. Laaksonen R. On the mechanisms of statin-induced myopathy. Clin. Pharmacol. Ther. 2006, 79:529-531.
5. Buettner C., Davis R.B., Leveille S.G., Mittleman M.A., Mukamal K.J. Prevalence of musculoskeletal pain and statin use. J. Gen. Intern. Med. 2008, 23:1182-1186.
6. Graham D.J., Staffa J.A., Shatin D., Andrade S.E., Schech S.D., La Grenade L., Gurwitz J.H., Chan K.A., Goodman M.J., Platt R. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 2004, 292:2585-2590.
7. Link E., Parish S., Armitage J., Bowman L., Heath S., Matsuda F., Gut I., Lathrop M., Collins R. SLCO1B1 variants and statin-induced myopathy-a genomewide study. N. Engl. J. Med. 2008, 359:789-799.
8. Kaufmann P., Torok M., Zahno A., Waldhauser K.M., Brecht K., Krahenbuhl S. Toxicity of statins on rat skeletal muscle mitochondria. Cell. Mol. Life Sci. 2006, 63:2415-2425.
9. Kwak H.B., Thalacker-Mercer A., Anderson E.J., Lin C.T., Kane D.A., Lee N.S., Cortright R.N., Bamman M.M., Neufer P.D. Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes. Free Radic. Biol. Med. 2012, 52:198-207.
10. Hanai J., Cao P., Tanksale P., Imamura S., Koshimizu E., Zhao J., Kishi S., Yamashita M., Phillips P.S., Sukhatme V.P., Lecker S.H. The muscle-specific ubiquitin ligase atrogin-1/MAFbx mediates statin-induced muscle toxicity. J. Clin. Invest. 2007, 117:3940-3951.
11. Tuckow A.P., Jefferson S.J., Kimball S.R., Jefferson L.S. Simvastatin represses protein synthesis in the muscle-derived C(2)C(1)(2) cell line with a concomitant reduction in eukaryotic initiation factor 2B expression. Am. J. Physiol. Endocrinol. Metab. 2011, 300:E564-E570.
12. Sakamoto K., Wada I., Kimura J. Inhibition of Rab1 GTPase and endoplasmic reticulum-to-Golgi trafficking underlies statin's toxicity in rat skeletal myofibers. J. Pharmacol. Exp. Ther. 2011, 338:62-69.
13. Mangravite L.M., Engelhardt B.E., Medina M.W., Smith J.D., Brown C.D., Chasman D.I., Mecham B.H., Howie B., Shim H., Naidoo D., Feng Q., Rieder M.J., Chen Y.D., Rotter J.I., Ridker P.M., Hopewell J.C., Parish S., Armitage J., Collins R., Wilke R.A., Nickerson D.A., Stephens M., Krauss R.M. A statin-dependent QTL for GATM expression is associated with statin-induced myopathy. Nature 2013, 502:377-380.
14. Mullen P.J., Zahno A., Lindinger P., Maseneni S., Felser A., Krahenbuhl S., Brecht K. Susceptibility to simvastatin-induced toxicity is partly determined by mitochondrial respiration and phosphorylation state of Akt. Biochim. Biophys. Acta, Mol. Cell Res. 2011, 1813:2079-2087.
15. Schiaffino S., Mammucari C. Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models. Skelet. Muscle 2011, 1:4.
16. Crossland H., Constantin-Teodosiu D., Gardiner S.M., Constantin D., Greenhaff P.L. A potential role for Akt/FOXO signalling in both protein loss and the impairment of muscle carbohydrate oxidation during sepsis in rodent skeletal muscle. J. Physiol. Lond. 2008, 586:5589-5600.
17. Zhou H.L., Li X.M., Meinkoth J., Pittman R.N. Akt regulates cell survival and apoptosis at a postmitochondrial level. J. Cell Biol. 2000, 151:483-494.
18. Magnuson B., Ekim B., Fingar D.C. Regulation and function of ribosomal protein S6 kinase (S6K) within mTOR signalling networks. Biochem. J. 2012, 441:1-21.
19. Gingras A.C., Kennedy S.G., O'Leary M.A., Sonenberg N., Hay N. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev. 1998, 12:502-513.
20. Clavel S., Siffroi-Fernandez S., Coldefy A.S., Boulukos K., Pisani D.F., Derijard B. Regulation of the intracellular localization of Foxo3a by stress-activated protein kinase signaling pathways in skeletal muscle cells. Mol. Cell. Biol. 2010, 30:470-480.
21. Bodine S.C., Latres E., Baumhueter S., Lai V.K.M., Nunez L., Clarke B.A., Poueymirou W.T., Panaro F.J., Na E.Q., Dharmarajan K., Pan Z.Q., Valenzuela D.M., DeChiara T.M., Stitt T.N., Yancopoulos G.D., Glass D.J. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 2001, 294:1704-1708.
22. Sandri M., Sandri C., Gilbert A., Skurk C., Calabria E., Picard A., Walsh K., Schiaffino S., Lecker S.H., Goldberg A.L. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 2004, 117:399-412.
23. Bogman K., Peyer A.K., Torok M., Kusters E., Drewe J. HMG-CoA reductase inhibitors and P-glycoprotein modulation. Br. J. Pharmacol. 2001, 132:1183-1192.
24. Waldhauser K.M., Torok M., Ha H.R., Thomet U., Konrad D., Brecht K., Follath F., Krahenbuhl S. Hepatocellular toxicity and pharmacological effect of amiodarone and amiodarone derivatives. J. Pharmacol. Exp. Ther. 2006, 319:1413-1423.
25. Minetti G.C., Feige J.N., Bombard F., Heier A., Morvan F., Nurnberg B., Leiss V., Birnbaumer L., Glass D.J., Fornaro M. Galphai2 signaling is required for skeletal muscle growth, regeneration, and satellite cell proliferation and differentiation. Mol. Cell. Biol. 2014, 34:619-630.
26. Stitt T.N., Drujan D., Clarke B.A., Panaro F., Timofeyva Y., Kline W.O., Gonzalez M., Yancopoulos G.D., Glass D.J. The IGF-1/PI3K/Akt pathway prevents expression of muscle atrophy-induced ubiquitin ligases by inhibiting FOXO transcription factors. Mol. Cell 2004, 14:395-403.
27. Laplante M., Sabatini D.M. mTOR signalling at a glance. J. Cell. Sci. 2009, 122:3589-3594.
28. Kennedy S.G., Wagner A.J., Conzen S.D., Jordan J., Bellacosa A., Tsichlis P.N., Hay N. The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev. 1997, 11:701-713.
29. Gray D.F., Bundgaard H., Hansen P.S., Buhagiar K.A., Mihailidou A.S., Jessup W., Kjeldsen K., Rasmussen H.H. HMG CoA reductase inhibition reduces sarcolemmal Na(+)-K(+) pump density. Cardiovasc. Res. 2000, 47:329-335.
30. Mullen P.J., Luscher B., Scharnagl H., Krahenbuhl S., Brecht K. Effect of simvastatin on cholesterol metabolism in C2C12 myotubes and HepG2 cells, and consequences for statin-induced myopathy. Biochem. Pharmacol. 2010, 79:1200-1209.
31. Baviera A.M., Zanon N.M., Navegantes L.C., Kettelhut I.C. Involvement of cAMP/Epac/PI3K-dependent pathway in the antiproteolytic effect of epinephrine on rat skeletal muscle. Mol. Cell. Endocrinol. 2010, 315:104-112.
32. Bouitbir J., Charles A.L., Echaniz-Laguna A., Kindo M., Daussin F., Auwerx J., Piquard F., Geny B., Zoll J. Opposite effects of statins on mitochondria of cardiac and skeletal muscles: a 'mitohormesis' mechanism involving reactive oxygen species and PGC-1. Eur. Heart J. 2012, 33:1397-1407.
33. Sirvent P., Mercier J., Vassort G., Lacampagne A. Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle. Biochem. Biophys. Res. Commun. 2005, 329:1067-1075.
34. Slade J.M., Delano M.C., Meyer R.A. Elevated skeletal muscle phosphodiesters in adults using statin medications. Muscle Nerve 2006, 34:782-784.
35. Bonifacio A., Mullen P.J., Mityko I.S., Navegantes L.C., Bouitbir J., Krahenbuh S. Simvastatin induces mitochondrial dysfunction and increased atrogin-1 expression in H9c2 cardiomyocytes and mice in vivo. Arch. Toxicol. 2014, [Epub ahead of print].
36. Sarbassov D.D., Guertin D.A., Ali S.M., Sabatin D.M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science (New York, N.Y.) 2005, 307:1098-1101.
37. Ma X.M., Blenis J. Molecular mechanisms of mTOR-mediated translational control, nature reviews. Mol. Cell Biol. 2009, 10:307-318.
38. Roudier E., Mistafa O., Stenius U. Statins induce mammalian target of rapamycin (mTOR)-mediated inhibition of Akt signaling and sensitize p53-deficient cells to cytostatic drugs. Mol. Cancer Ther. 2006, 5:2706-2715.
39. Kasliwal R., Wilton L.V., Cornelius V., Aurich-Barrera B., Shakir S.A. Safety profile of rosuvastatin: results of a prescription-event monitoring study of 11,680 patients. Drug Saf.: an international journal of medical toxicology and drug experience 2007, 30:157-170.
40. 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, 154:1482-1490.
41. Higgins J.W., Bao J.Q., Ke A.B., Manro J.R., Fallon J.K., Smith P.C., Zamek-Gliszczynski M.J. Utility of Oatp1a/1b-knockout and OATP1B1/3-humanized mice in the study of OATP-mediated pharmacokinetics and tissue distribution: case studies with pravastatin, atorvastatin, simvastatin, and carboxydichlorofluorescein. Drug Metab. Dispos. the biological fate of chemicals 2014, 42:182-192.
42. Neuvonen P.J., Kantola T., Kivisto K.T. Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin. Pharmacol. Ther. 1998, 63:332-341.
43. Tsivgoulis G., Spengos K., Karandreas N., Panas M., Kladi A., Manta P. Presymptomatic neuromuscular disorders disclosed following statin treatment. Arch. Intern. Med. 2006, 166:1519-1524.
44. Vladutiu G.D., Simmons Z., Isackson P.J., Tarnopolsky M., Peltier W.L., Barboi A.C., Sripathi N., Wortmann R.L., Phillips P.S. Genetic risk factors associated with lipid-lowering drug-induced myopathies. Muscle Nerve 2006, 34:153-162.
45. Ratz Bravo A.E., Tchambaz L., Krahenbuhl-Melcher A., Hess L., Schlienger R.G., Krahenbuhl S. Prevalence of potentially severe drug-drug interactions in ambulatory patients with dyslipidaemia receiving HMG-CoA reductase inhibitor therapy. Drug Saf.: an international journal of medical toxicology and drug experience 2005, 28:263-275.
46. Roten L., Schoenenberger R.A., Krahenbuhl S., Schlienger R.G. Rhabdomyolysis in association with simvastatin and amiodarone. Ann. Pharmacother. 2004, 38:978-981.