Molecular and cellular mechanisms of skeletal muscle atrophy: An update

Journal of Cachexia, Sarcopenia and Muscle

Volumn 3, Issue 3, 2012, Pages 163-179

  Fanzani, Alessandro ^a   Conraads, Viviane M ^b,c   Penna, Fabio ^d   Martinet, Wim ^c  

^a UNIVERSITY OF BRESCIA   (Italy)

^b ANTWERP UNIVERSITY HOSPITAL   (Belgium)

^c UNIVERSITY OF ANTWERP   (Belgium)

^d UNIVERSITY OF BARCELONA   (Spain)

Author keywords

Apoptosis; Autophagy; Cachexia; Proteasome; Skeletal muscle atrophy; Therapy

Indexed keywords

ATROGIN 1; CATHEPSIN L; GROWTH HORMONE; HISTONE DEACETYLASE 4; HISTONE DEACETYLASE 5; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDUCIBLE NITRIC OXIDE SYNTHASE; INSULIN; INSULIN RECEPTOR SUBSTRATE 1; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; MITOGEN ACTIVATED PROTEIN KINASE P38; MYOSTATIN; NEURONAL NITRIC OXIDE SYNTHASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; REACTIVE OXYGEN METABOLITE; S6 KINASE; SIALIDASE; SMAD2 PROTEIN; SMAD3 PROTEIN; SOMATOMEDIN C; TESTOSTERONE; TRANSCRIPTION FACTOR FKHRL1; TRANSCRIPTION FACTOR FOXO; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; UBIQUITIN PROTEIN LIGASE E3;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; AGING; AMYOTROPHIC LATERAL SCLEROSIS; APOPTOSIS; AUTOPHAGY; BURN; CACHEXIA; CELL DIFFERENTIATION; CELL PROLIFERATION; CHRONIC OBSTRUCTIVE LUNG DISEASE; DUCHENNE MUSCULAR DYSTROPHY; DYSTROPHY; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; HEART FAILURE; HUMAN; IMMOBILIZATION; IMMUNOPATHOLOGY; INSULIN RESISTANCE; KIDNEY FAILURE; MALNUTRITION; MUSCLE ATROPHY; MUSCLE DENERVATION; MUSCLE FORCE; MUSCLE MASS; MUSCLE REGENERATION; NEOPLASM; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN SYNTHESIS; REVIEW; SEPSIS; SIGNAL TRANSDUCTION; SKELETAL MUSCLE;

EID: 84865799919     PISSN: 21905991     EISSN: 21906009     Source Type: Journal    
DOI: 10.1007/s13539-012-0074-6     Document Type: Review

References (251)

1. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, Boirie Y, Cederholm T, Landi F, et al. People EWGoSiO. Sarcopenia: European consensus on definition and diagnosis: report of the European Working Group on sarcopenia in older people. Age Ageing. 2010; 39: 412-23.
2. Thomas DR. Loss of skeletal muscle mass in aging: examining the relationship of starvation, sarcopenia and cachexia. Clin Nutr. 2007; 26: 389-99.
3. Vandervoort AA. Aging of the human neuromuscular system. Muscle Nerve. 2002; 25: 17-25.
4. Dedkov EI, Borisov AB, Carlson BM. Dynamics of postdenervation atrophy of young and old skeletal muscles: differential responses of fiber types and muscle types. J Gerontol A Biol Sci Med Sci. 2003; 58: 984-91.
5. Williams AD, Selig S, Hare DL, Hayes A, Krum H, Patterson J, et al. Reduced exercise tolerance in CHF may be related to factors other than impaired skeletal muscle oxidative capacity. J Card Fail. 2004; 10: 141-8.
6. Massie BM, Simonini A, Sahgal P, Wells L, Dudley GA. Relation of systemic and local muscle exercise capacity to skeletal muscle characteristics in men with congestive heart failure. J Am Coll Cardiol. 1996; 27: 140-5.
7. Schaufelberger M, Eriksson BO, Lönn L, Rundqvist B, Sunnerhagen KS, Swedberg K. Skeletal muscle characteristics, muscle strength and thigh muscle area in patients before and after cardiac transplantation. Eur J Heart Fail. 2001; 3: 59-67.
8. Harrington D, Anker SD, Chua TP, Webb-Peploe KM, Ponikowski PP, Poole-Wilson PA, et al. Skeletal muscle function and its relation to exercise tolerance in chronic heart failure. J Am Coll Cardiol. 1997; 30: 1758-64.
9. Anker SD, Ponikowski P, Varney S, Chua TP, Clark AL, Webb-Peploe KM, et al. Wasting as independent risk factor for mortality in chronic heart failure. Lancet. 1997; 349: 1050-3.
10. Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011; 12: 489-95.
11. Florini JR, Ewton DZ, Magri KA. Hormones, growth factors, and myogenic differentiation. Annu Rev Physiol. 1991; 53: 201-16.
12. Coleman ME, DeMayo F, Yin KC, Lee HM, Geske R, Montgomery C, et al. Myogenic vector expression of insulin-like growth factor I stimulates muscle cell differentiation and myofiber hypertrophy in transgenic mice. J Biol Chem. 1995; 270: 12109-16.
13. Musarò A, McCullagh K, Paul A, Houghton L, Dobrowolny G, Molinaro M, et al. Localized Igf-1 transgene expression sustains hypertrophy and regeneration in senescent skeletal muscle. Nat Genet. 2001; 27: 195-200.
14. Stewart CE, Rotwein P. Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Physiol Rev. 1996; 76: 1005-26.
15. Harridge SD. Ageing and local growth factors in muscle. Scand J Med Sci Sports. 2003; 13: 34-9.
16. Niebauer J, Pflaum CD, Clark AL, Strasburger CJ, Hooper J, Poole-Wilson PA, et al. Deficient insulin-like growth factor I in chronic heart failure predicts altered body composition, anabolic deficiency, cytokine and neurohormonal activation. J Am Coll Cardiol. 1998; 32: 393-7.
17. Costelli P, Muscaritoli M, Bossola M, Penna F, Reffo P, Bonetto A, et al. Rossi Fanelli F. IGF-1 is downregulated in experimental cancer cachexia. Am J Physiol Regul Integr Comp Physiol. 2006; 291: R674-83.
18. Jankowska EA, Biel B, Majda J, Szklarska A, Lopuszanska M, Medras M, et al. Anabolic deficiency in men with chronic heart failure: prevalence and detrimental impact on survival. Circulation. 2006; 114: 1829-37.
19. Yakar S, Liu JL, Le Roith D. The growth hormone/insulin-like growth factor-I system: implications for organ growth and development. Pediatr Nephrol. 2000; 14: 544-9.
20. Yakar S, Liu JL, Fernandez AM, Wu Y, Schally AV, Frystyk J, et al. Liver-specific igf-1 gene deletion leads to muscle insulin insensitivity. Diabetes. 2001; 50: 1110-8.
21. Pelosi L, Giacinti C, Nardis C, Borsellino G, Rizzuto E, Nicoletti C, et al. Local expression of IGF-1 accelerates muscle regeneration by rapidly modulating inflammatory cytokines and chemokines. FASEB J. 2007; 21: 1393-402.
22. Denti MA, Rosa A, D'Antona G, Sthandier O, De Angelis FG, Nicoletti C, et al. Body-wide gene therapy of Duchenne muscular dystrophy in the mdx mouse model. Proc Natl Acad Sci U S A. 2006; 103: 3758-63.
23. Barton ER, Morris L, Musaro A, Rosenthal N, Sweeney HL. Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice. J Cell Biol. 2002; 157: 137-48.
24. Dobrowolny G, Giacinti C, Pelosi L, Nicoletti C, Winn N, Barberi L, et al. Muscle expression of a local Igf-1 isoform protects motor neurons in an ALS mouse model. J Cell Biol. 2005; 168: 193-9.
25. Palazzolo I, Stack C, Kong L, Musaro A, Adachi H, Katsuno M, et al. Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy. Neuron. 2009; 63: 316-28.
26. Sandri M. Signaling in muscle atrophy and hypertrophy. Physiology (Bethesda). 2008; 23: 160-70.
27. Glass DJ. Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol. 2005; 37: 1974-84.
28. Glass DJ. Signaling pathways perturbing muscle mass. Curr Opin Clin Nutr Metab Care. 2010; 13: 225-9.
29. Price SR, Bailey JL, Wang X, Jurkovitz C, England BK, Ding X, et al. Muscle wasting in insulinopenic rats results from activation of the ATP-dependent, ubiquitin-proteasome proteolytic pathway by a mechanism including gene transcription. J Clin Invest. 1996; 98: 1703-8.
30. Fernández AM, Kim JK, Yakar S, Dupont J, Hernandez-Sanchez C, Castle AL, et al. Functional inactivation of the IGF-I and insulin receptors in skeletal muscle causes type 2 diabetes. Genes Dev. 2001; 15: 1926-34.
31. Balagopal P, Proctor D, Nair KS. Sarcopenia and hormonal changes. Endocrine. 1997; 7: 57-60.
32. Guillet C, Prod'homme M, Balage M, Gachon P, Giraudet C, Morin L, et al. Impaired anabolic response of muscle protein synthesis is associated with S6K1 dysregulation in elderly humans. FASEB J. 2004; 18: 1586-7.
33. García-Martínez C, López-Soriano FJ, Argilés JM. Acute treatment with tumour necrosis factor-alpha induces changes in protein metabolism in rat skeletal muscle. Mol Cell Biochem. 1993; 125: 11-8.
34. García-Martínez C, Llovera M, Agell N, López-Soriano FJ, Argilés JM. Ubiquitin gene expression in skeletal muscle is increased by tumour necrosis factor-alpha. Biochem Biophys Res Commun. 1994; 201: 682-6.
35. Lee SJ, Lee YS, Zimmers TA, Soleimani A, Matzuk MM, Tsuchida K, et al. Regulation of muscle mass by follistatin and activins. Mol Endocrinol. 2010; 24: 1998-2008.
36. Gilson H, Schakman O, Kalista S, Lause P, Tsuchida K, Thissen JP. Follistatin induces muscle hypertrophy through satellite cell proliferation and inhibition of both myostatin and activin. Am J Physiol Endocrinol Metab. 2009; 297: E157-64.
37. McPherron AC, Lee SJ. Double muscling in cattle due to mutations in the myostatin gene. Proc Natl Acad Sci U S A. 1997; 94: 12457-61.
38. McPherron AC, Lawler AM, Lee SJ. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 1997; 387: 83-90.
39. Combaret L, Taillandier D, Dardevet D, Béchet D, Rallière C, Claustre A, et al. Glucocorticoids regulate mRNA levels for subunits of the 19 S regulatory complex of the 26 S proteasome in fast-twitch skeletal muscles. Biochem J. 2004; 378: 239-46.
40. Wing SS, Goldberg AL. Glucocorticoids activate the ATP-ubiquitin-dependent proteolytic system in skeletal muscle during fasting. Am J Physiol. 1993; 264: E668-76.
41. Chrysis D, Underwood LE. Regulation of components of the ubiquitin system by insulin-like growth factor I and growth hormone in skeletal muscle of rats made catabolic with dexamethasone. Endocrinology. 1999; 140: 5635-41.
42. Dehoux M, van Beneden R, Pasko N, Lause P, Verniers J, Underwood L, et al. Role of the insulin-like growth factor I decline in the induction of atrogin-1/MAFbx during fasting and diabetes. Endocrinology. 2004; 145: 4806-12.
43. Llovera M, García-Martínez C, López-Soriano J, Agell N, López-Soriano FJ, Garcia I, et al. Protein turnover in skeletal muscle of tumour-bearing transgenic mice overexpressing the soluble TNF receptor-1. Cancer Lett. 1998; 130: 19-27.
44. Jagoe RT, Goldberg AL. What do we really know about the ubiquitin-proteasome pathway in muscle atrophy? Curr Opin Clin Nutr Metab Care. 2001; 4: 183-90.
45. Tsujinaka T, Fujita J, Ebisui C, Yano M, Kominami E, Suzuki K, et al. Interleukin 6 receptor antibody inhibits muscle atrophy and modulates proteolytic systems in interleukin 6 transgenic mice. J Clin Invest. 1996; 97: 244-9.
46. Janssen SP, Gayan-Ramirez G, van den Bergh A, Herijgers P, Maes K, Verbeken E, et al. Interleukin-6 causes myocardial failure and skeletal muscle atrophy in rats. Circulation. 2005; 111: 996-1005.
47. Zimmers TA, Davies MV, Koniaris LG, Haynes P, Esquela AF, Tomkinson KN, et al. Induction of cachexia in mice by systemically administered myostatin. Science. 2002; 296: 1486-8.
48. Schakman O, Gilson H, Kalista S, Thissen JP. Mechanisms of muscle atrophy induced by glucocorticoids. Horm Res. 2009; 72: 36-41.
49. Powers SK, Kavazis AN, McClung JM. Oxidative stress and disuse muscle atrophy. J Appl Physiol. 2007; 102: 2389-97.
50. Glass DJ. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat Cell Biol. 2003; 5: 87-90.
51. Lee SJ, Glass DJ. Treating cancer cachexia to treat cancer. Skelet Muscle. 2011; 1: 2.
52. Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, et al. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nat Cell Biol. 2001; 3: 1009-13.
53. Stitt TN, Drujan D, Clarke BA, Panaro F, Timofeyva Y, Kline WO, et al. 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.
54. Sandri M, Sandri C, Gilbert A, Skurk C, Calabria E, Picard A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell. 2004; 117: 399-412.
55. Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat Cell Biol. 2001; 3: 1014-9.
56. Mammucari C, Milan G, Romanello V, Masiero E, Rudolf R, Del Piccolo P, et al. FoxO3 controls autophagy in skeletal muscle in vivo. Cell Metab. 2007; 6: 458-71.
57. Zhao J, Brault JJ, Schild A, Cao P, Sandri M, Schiaffino S, et al. FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab. 2007; 6: 472-83.
58. Blaauw B, Canato M, Agatea L, Toniolo L, Mammucari C, Masiero E, et al. Inducible activation of Akt increases skeletal muscle mass and force without satellite cell activation. FASEB J. 2009; 23: 3896-905.
59. Lai KM, Gonzalez M, Poueymirou WT, Kline WO, Na E, Zlotchenko E, et al. Conditional activation of akt in adult skeletal muscle induces rapid hypertrophy. Mol Cell Biol. 2004; 24: 9295-304.
60. Peng XD, Xu PZ, Chen ML, Hahn-Windgassen A, Skeen J, Jacobs J, et al. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes Dev. 2003; 17: 1352-65.
61. Ohanna M, Sobering AK, Lapointe T, Lorenzo L, Praud C, Petroulakis E, et al. Atrophy of S6K1(-/-) skeletal muscle cells reveals distinct mTOR effectors for cell cycle and size control. Nat Cell Biol. 2005; 7: 286-94.
62. Léger B, Vergani L, Sorarù G, Hespel P, Derave W, Gobelet C, et al. Human skeletal muscle atrophy in amyotrophic lateral sclerosis reveals a reduction in Akt and an increase in atrogin-1. FASEB J. 2006; 20: 583-5.
63. Dobrowolny G, Aucello M, Rizzuto E, Beccafico S, Mammucari C, Boncompagni S, et al. Skeletal muscle is a primary target of SOD1G93A-mediated toxicity. Cell Metab. 2008; 8: 425-36.
64. Dobrowolny G, Aucello M, Musarò A. Muscle atrophy induced by SOD1G93A expression does not involve the activation of caspase in the absence of denervation. Skelet Muscle. 2011; 1: 3.
65. Price SR, Gooch JL, Donaldson SK, Roberts-Wilson TK. Muscle atrophy in chronic kidney disease results from abnormalities in insulin signaling. J Ren Nutr. 2010; 20: S24-8.
66. Zhang L, Wang XH, Wang H, Du J, Mitch WE. Satellite cell dysfunction and impaired IGF-1 signaling cause CKD-induced muscle atrophy. J Am Soc Nephrol. 2010; 21: 419-27.
67. Favier FB, Costes F, Defour A, Bonnefoy R, Lefai E, Baugé S, et al. Downregulation of Akt/mammalian target of rapamycin pathway in skeletal muscle is associated with increased REDD1 expression in response to chronic hypoxia. Am J Physiol Regul Integr Comp Physiol. 2010; 298: R1659-66.
68. Mallinson JE, Constantin-Teodosiu D, Sidaway J, Westwood FR, Greenhaff PL. Blunted Akt/FOXO signalling and activation of genes controlling atrophy and fuel use in statin myopathy. J Physiol. 2009; 587: 219-30.
69. Crossland H, Constantin-Teodosiu D, Gardiner SM, Constantin D, Greenhaff PL. 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. 2008; 586: 5589-600.
70. Smith IJ, Lecker SH, Hasselgren PO. Calpain activity and muscle wasting in sepsis. Am J Physiol Endocrinol Metab. 2008; 295: E762-71.
71. Sugita H, Kaneki M, Sugita M, Yasukawa T, Yasuhara S, Martyn JA. Burn injury impairs insulin-stimulated Akt/PKB activation in skeletal muscle. Am J Physiol Endocrinol Metab. 2005; 288: E585-91.
72. Penna F, Bonetto A, Muscaritoli M, Costamagna D, Minero VG, Bonelli G, et al. Muscle atrophy in experimental cancer cachexia: is the IGF-1 signaling pathway involved? Int J Cancer. 2010; 127: 1706-17.
73. Sishi BJ, Engelbrecht AM. Tumor necrosis factor alpha (TNF-α) inactivates the PI3-kinase/PKB pathway and induces atrophy and apoptosis in L6 myotubes. Cytokine. 2011; 54: 173-84.
74. Dogra C, Changotra H, Wedhas N, Qin X, Wergedal JE, Kumar A. TNF-related weak inducer of apoptosis (TWEAK) is a potent skeletal muscle-wasting cytokine. FASEB J. 2007; 21: 1857-69.
75. Zheng B, Ohkawa S, Li H, Roberts-Wilson TK, Price SR. FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. FASEB J. 2010; 24: 2660-9.
76. Zhao W, Qin W, Pan J, Wu Y, Bauman WA, Cardozo C. Dependence of dexamethasone-induced Akt/FOXO1 signaling, upregulation of MAFbx, and protein catabolism upon the glucocorticoid receptor. Biochem Biophys Res Commun. 2009; 378: 668-72.
77. Zhang L, Du J, Hu Z, Han G, Delafontaine P, Garcia G, et al. IL-6 and serum amyloid A synergy mediates angiotensin II-induced muscle wasting. J Am Soc Nephrol. 2009; 20: 604-12.
78. Fanzani A, Zanola A, Rovetta F, Rossi S, Aleo MF. Cisplatin triggers atrophy of skeletal C2C12 myotubes via impairment of Akt signalling pathway and subsequent increment activity of proteasome and autophagy systems. Toxicol Appl Pharmacol. 2011; 250: 312-21.
79. Lokireddy S, McFarlane C, Ge X, Zhang H, Sze SK, Sharma M, et al. Myostatin induces degradation of sarcomeric proteins through a Smad3 signaling mechanism during skeletal muscle wasting. Mol Endocrinol. 2011; 25: 1936-49.
80. Lokireddy S, Mouly V, Butler-Browne G, Gluckman PD, Sharma M, Kambadur R, McFarlane C. Myostatin promotes the wasting of human myoblast cultures through promoting ubiquitin-proteasome pathway-mediated loss of sarcomeric proteins. Am J Physiol Cell Physiol. 2011; 301: C1316-24.
81. Trendelenburg AU, Meyer A, Rohner D, Boyle J, Hatakeyama S, Glass DJ. Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am J Physiol Cell Physiol. 2009; 296: C1258-70.
82. Amirouche A, Durieux AC, Banzet S, Koulmann N, Bonnefoy R, Mouret C, et al. Down-regulation of Akt/mammalian target of rapamycin signaling pathway in response to myostatin overexpression in skeletal muscle. Endocrinology. 2009; 150: 286-94.
83. Morissette MR, Cook SA, Buranasombati C, Rosenberg MA, Rosenzweig A. Myostatin inhibits IGF-I-induced myotube hypertrophy through Akt. Am J Physiol Cell Physiol. 2009; 297: C1124-32.
84. Peter AK, Crosbie RH. Hypertrophic response of Duchenne and limb-girdle muscular dystrophies is associated with activation of Akt pathway. Exp Cell Res. 2006; 312: 2580-91.
85. Gurpur PB, Liu J, Burkin DJ, Kaufman SJ. Valproic acid activates the PI3K/Akt/mTOR pathway in muscle and ameliorates pathology in a mouse model of Duchenne muscular dystrophy. Am J Pathol. 2009; 174: 999-1008.
86. Blaauw B, Mammucari C, Toniolo L, Agatea L, Abraham R, Sandri M, et al. Akt activation prevents the force drop induced by eccentric contractions in dystrophin-deficient skeletal muscle. Hum Mol Genet. 2008; 17: 3686-96.
87. Peter AK, Ko CY, Kim MH, Hsu N, Ouchi N, Rhie S, et al. Myogenic Akt signaling upregulates the utrophin-glycoprotein complex and promotes sarcolemma stability in muscular dystrophy. Hum Mol Genet. 2009; 18: 318-27.
88. Kim MH, Kay DI, Rudra RT, Chen BM, Hsu N, Izumiya Y, et al. Myogenic Akt signaling attenuates muscular degeneration, promotes myofiber regeneration and improves muscle function in dystrophin-deficient mdx mice. Hum Mol Genet. 2011; 20: 1324-38.
89. Dahiya S, Bhatnagar S, Hindi SM, Jiang C, Paul PK, Kuang S, et al. Elevated levels of active matrix metalloproteinase-9 cause hypertrophy in skeletal muscle of normal and dystrophin-deficient mdx mice. Hum Mol Genet. 2011; 20: 4345-59.
90. Kumar A, Bhatnagar S. Matrix metalloproteinase inhibitor batimastat alleviates pathology and improves skeletal muscle function in dystrophin-deficient mdx mice. Am J Pathol. 2010; 177: 248-60.
91. Kandarian SC, Jackman RW. Intracellular signaling during skeletal muscle atrophy. Muscle Nerve. 2006; 33: 155-65.
92. Jackman RW, Kandarian SC. The molecular basis of skeletal muscle atrophy. Am J Physiol Cell Physiol. 2004; 287: C834-43.
93. Yaron A, Hatzubai A, Davis M, Lavon I, Amit S, Manning AM, et al. Identification of the receptor component of the IkappaBalpha-ubiquitin ligase. Nature. 1998; 396: 590-4.
94. Hunter RB, Stevenson E, Koncarevic A, Mitchell-Felton H, Essig DA, Kandarian SC. Activation of an alternative NF-kappaB pathway in skeletal muscle during disuse atrophy. FASEB J. 2002; 16: 529-38.
95. Cai D, Frantz JD, Tawa NE, Melendez PA, Oh BC, Lidov HG, et al. IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell. 2004; 119: 285-98.
96. Buck M, Chojkier M. Muscle wasting and dedifferentiation induced by oxidative stress in a murine model of cachexia is prevented by inhibitors of nitric oxide synthesis and antioxidants. EMBO J. 1996; 15: 1753-65.
97. Di Marco S, Mazroui R, Dallaire P, Chittur S, Tenenbaum SA, Radzioch D, et al. NF-kappa B-mediated MyoD decay during muscle wasting requires nitric oxide synthase mRNA stabilization, HuR protein, and nitric oxide release. Mol Cell Biol. 2005; 25: 6533-45.
98. Li YP, Reid MB. NF-kappaB mediates the protein loss induced by TNF-alpha in differentiated skeletal muscle myotubes. Am J Physiol Regul Integr Comp Physiol. 2000; 279: R1165-70.
99. Williams G, Brown T, Becker L, Prager M, Giroir BP. Cytokine-induced expression of nitric oxide synthase in C2C12 skeletal muscle myocytes. Am J Physiol. 1994; 267: R1020-5.
100. Kanski J, Hong SJ, Schöneich C. Proteomic analysis of protein nitration in aging skeletal muscle and identification of nitrotyrosine-containing sequences in vivo by nanoelectrospray ionization tandem mass spectrometry. J Biol Chem. 2005; 280: 24261-6.
101. Viner RI, Ferrington DA, Hühmer AF, Bigelow DJ, Schöneich C. Accumulation of nitrotyrosine on the SERCA2a isoform of SR Ca-ATPase of rat skeletal muscle during aging: a peroxynitrite-mediated process? FEBS Lett. 1996; 379: 286-90.
102. Haynes V, Traaseth NJ, Elfering S, Fujisawa Y, Giulivi C. Nitration of specific tyrosines in FoF1 ATP synthase and activity loss in aging. Am J Physiol Endocrinol Metab. 2010; 298: E978-87.
103. Beal MF. Oxidatively modified proteins in aging and disease. Free Radic Biol Med. 2002; 32: 797-803.
104. Braga M, Sinha Hikim AP, Datta S, Ferrini MG, Brown D, Kovacheva EL, et al. Involvement of oxidative stress and caspase 2-mediated intrinsic pathway signaling in age-related increase in muscle cell apoptosis in mice. Apoptosis. 2008; 13: 822-32.
105. Frost RA, Nystrom GJ, Lang CH. Endotoxin and interferon-gamma inhibit translation in skeletal muscle cells by stimulating nitric oxide synthase activity. Shock. 2009; 32: 416-26.
106. Agustí A, Morlá M, Sauleda J, Saus C, Busquets X. NF-kappaB activation and iNOS upregulation in skeletal muscle of patients with COPD and low body weight. Thorax. 2004; 59: 483-7.
107. Ramamoorthy S, Donohue M, Buck M. Decreased Jun-D and myogenin expression in muscle wasting of human cachexia. Am J Physiol Endocrinol Metab. 2009; 297: E392-401.
108. Finanger Hedderick EL, Simmers JL, Soleimani A, Andres-Mateos E, Marx R, Files DC, et al. Loss of sarcolemmal nNOS is common in acquired and inherited neuromuscular disorders. Neurology. 2011; 76: 960-7.
109. Suzuki N, Mizuno H, Warita H, Takeda S, Itoyama Y, Aoki M. Neuronal NOS is dislocated during muscle atrophy in amyotrophic lateral sclerosis. J Neurol Sci. 2010; 294: 95-101.
110. Suzuki N, Motohashi N, Uezumi A, Fukada S, Yoshimura T, Itoyama Y, et al. NO production results in suspension-induced muscle atrophy through dislocation of neuronal NOS. J Clin Invest. 2007; 117: 2468-76.
111. Hall DT, Ma JF, Marco SD, Gallouzi IE. Inducible nitric oxide synthase (iNOS) in muscle wasting syndrome, sarcopenia, and cachexia. Aging (Albany NY). 2011; 3: 702-15.
112. Jackson MJ. Free radicals generated by contracting muscle: by-products of metabolism or key regulators of muscle function? Free Radic Biol Med. 2008; 44: 132-41.
113. Kondo H, Miura M, Itokawa Y. Antioxidant enzyme systems in skeletal muscle atrophied by immobilization. Pflugers Arch. 1993; 422: 404-6.
114. Kondo H, Miura M, Itokawa Y. Oxidative stress in skeletal muscle atrophied by immobilization. Acta Physiol Scand. 1991; 142: 527-8.
115. Kondo H, Miura M, Nakagaki I, Sasaki S, Itokawa Y. Trace element movement and oxidative stress in skeletal muscle atrophied by immobilization. Am J Physiol. 1992; 262: E583-90.
116. Mastrocola R, Reffo P, Penna F, Tomasinelli CE, Boccuzzi G, Baccino FM, et al. Muscle wasting in diabetic and in tumor-bearing rats: role of oxidative stress. Free Radic Biol Med. 2008; 44: 584-93.
117. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev. 2002; 82: 373-428.
118. Chau V, Tobias JW, Bachmair A, Marriott D, Ecker DJ, Gonda DK, et al. A multiubiquitin chain is confined to specific lysine in a targeted short-lived protein. Science. 1989; 243: 1576-83.
119. Marmor MD, Yarden Y. Role of protein ubiquitylation in regulating endocytosis of receptor tyrosine kinases. Oncogene. 2004; 23: 2057-70.
120. Pickart CM. Ubiquitin enters the new millennium. Mol Cell. 2001; 8: 499-504.
121. Weissman AM. Themes and variations on ubiquitylation. Nat Rev Mol Cell Biol. 2001; 2: 169-78.
122. Bartke T, Pohl C, Pyrowolakis G, Jentsch S. Dual role of BRUCE as an antiapoptotic IAP and a chimeric E2/E3 ubiquitin ligase. Mol Cell. 2004; 14: 801-11.
123. Berleth ES, Pickart CM. Mechanism of ubiquitin conjugating enzyme E2-230 K: catalysis involving a thiol relay? Biochemistry. 1996; 35: 1664-71.
124. Bodine SC, Latres E, Baumhueter S, Lai VK, Nunez L, Clarke BA, et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science. 2001; 294: 1704-8.
125. Gomes MD, Lecker SH, Jagoe RT, Navon A, Goldberg AL. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A. 2001; 98: 14440-5.
126. Centner T, Yano J, Kimura E, McElhinny AS, Pelin K, Witt CC, et al. Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain. J Mol Biol. 2001; 306: 717-26.
127. McElhinny AS, Kakinuma K, Sorimachi H, Labeit S, Gregorio CC. Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and may have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1. J Cell Biol. 2002; 157: 125-36.
128. Clarke BA, Drujan D, Willis MS, Murphy LO, Corpina RA, Burova E, et al. The E3 Ligase MuRF1 degrades myosin heavy chain protein in dexamethasone-treated skeletal muscle. Cell Metab. 2007; 6: 376-85.
129. Schulze PC, Fang J, Kassik KA, Gannon J, Cupesi M, MacGillivray C, et al. Transgenic overexpression of locally acting insulin-like growth factor-1 inhibits ubiquitin-mediated muscle atrophy in chronic left-ventricular dysfunction. Circ Res. 2005; 97: 418-26.
130. Cohen S, Brault JJ, Gygi SP, Glass DJ, Valenzuela DM, Gartner C, et al. During muscle atrophy, thick, but not thin, filament components are degraded by MuRF1-dependent ubiquitylation. J Cell Biol. 2009; 185: 1083-95.
131. Tintignac LA, Lagirand J, Batonnet S, Sirri V, Leibovitch MP, Leibovitch SA. Degradation of MyoD mediated by the SCF (MAFbx) ubiquitin ligase. J Biol Chem. 2005; 280: 2847-56.
132. Lagirand-Cantaloube J, Offner N, Csibi A, Leibovitch MP, Batonnet-Pichon S, Tintignac LA, et al. The initiation factor eIF3-f is a major target for atrogin1/MAFbx function in skeletal muscle atrophy. EMBO J. 2008; 27: 1266-76.
133. Ekmark M, Rana ZA, Stewart G, Hardie DG, Gundersen K. De-phosphorylation of MyoD is linking nerve-evoked activity to fast myosin heavy chain expression in rodent adult skeletal muscle. J Physiol. 2007; 584: 637-50.
134. Goodman CA, Mabrey DM, Frey JW, Miu MH, Schmidt EK, Pierre P, et al. Novel insights into the regulation of skeletal muscle protein synthesis as revealed by a new nonradioactive in vivo technique. FASEB J. 2011; 25: 1028-39.
135. Krawiec BJ, Frost RA, Vary TC, Jefferson LS, Lang CH. Hindlimb casting decreases muscle mass in part by proteasome-dependent proteolysis but independent of protein synthesis. Am J Physiol Endocrinol Metab. 2005; 289: E969-80.
136. Fareed MU, Evenson AR, Wei W, Menconi M, Poylin V, Petkova V, et al. Treatment of rats with calpain inhibitors prevents sepsis-induced muscle proteolysis independent of atrogin-1/MAFbx and MuRF1 expression. Am J Physiol Regul Integr Comp Physiol. 2006; 290: R1589-97.
137. Dehoux M, Gobier C, Lause P, Bertrand L, Ketelslegers JM, Thissen JP. IGF-I does not prevent myotube atrophy caused by proinflammatory cytokines despite activation of Akt/Foxo and GSK-3beta pathways and inhibition of atrogin-1 mRNA. Am J Physiol Endocrinol Metab. 2007; 292: E145-50.
138. McLoughlin TJ, Smith SM, DeLong AD, Wang H, Unterman TG, Esser KA. FoxO1 induces apoptosis in skeletal myotubes in a DNA-binding-dependent manner. Am J Physiol Cell Physiol. 2009; 297: C548-55.
139. Senf SM, Dodd SL, Judge AR. FOXO signaling is required for disuse muscle atrophy and is directly regulated by Hsp70. Am J Physiol Cell Physiol. 2010; 298: C38-45.
140. Kudryashova E, Kudryashov D, Kramerova I, Spencer MJ. Trim32 is a ubiquitin ligase mutated in limb girdle muscular dystrophy type 2 H that binds to skeletal muscle myosin and ubiquitinates actin. J Mol Biol. 2005; 354: 413-24.
141. Locke M, Tinsley CL, Benson MA, Blake DJ. TRIM32 is an E3 ubiquitin ligase for dysbindin. Hum Mol Genet. 2009; 18: 2344-58.
142. Saccone V, Palmieri M, Passamano L, Piluso G, Meroni G, Politano L, et al. Mutations that impair interaction properties of TRIM32 associated with limb-girdle muscular dystrophy 2 H. Hum Mutat. 2008; 29: 240-7.
143. Kudryashova E, Wu J, Havton LA, Spencer MJ. Deficiency of the E3 ubiquitin ligase TRIM32 in mice leads to a myopathy with a neurogenic component. Hum Mol Genet. 2009; 18: 1353-67.
144. Ye J, Zhang Y, Xu J, Zhang Q, Zhu D. FBXO40, a gene encoding a novel muscle-specific F-box protein, is upregulated in denervation-related muscle atrophy. Gene. 2007; 404: 53-60.
145. Zhang Y, Ye J, Chen D, Zhao X, Xiao X, Tai S, et al. Differential expression profiling between the relative normal and dystrophic muscle tissues from the same LGMD patient. J Transl Med. 2006; 4: 53.
146. Shi J, Luo L, Eash J, Ibebunjo C, Glass DJ. The SCF-Fbxo40 Complex Induces IRS1 Ubiquitination in Skeletal Muscle, Limiting IGF1 Signaling. Dev Cell. 2011; 21: 835-47.
147. Lecker SH, Jagoe RT, Gilbert A, Gomes M, Baracos V, Bailey J, et al. Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J. 2004; 18: 39-51.
148. Kwon YT, Xia Z, Davydov IV, Lecker SH, Varshavsky A. Construction and analysis of mouse strains lacking the ubiquitin ligase UBR1 (E3alpha) of the N-end rule pathway. Mol Cell Biol. 2001; 21: 8007-21.
149. Lecker SH, Solomon V, Price SR, Kwon YT, Mitch WE, Goldberg AL. Ubiquitin conjugation by the N-end rule pathway and mRNAs for its components increase in muscles of diabetic rats. J Clin Invest. 1999; 104: 1411-20.
150. Wing SS, Bedard N. Insulin-like growth factor I stimulates degradation of an mRNA transcript encoding the 14 kDa ubiquitin-conjugating enzyme. Biochem J. 1996; 319: 455-61.
151. García-Martínez C, Agell N, Llovera M, López-Soriano FJ, Argilés JM. Tumour necrosis factor-alpha increases the ubiquitinization of rat skeletal muscle proteins. FEBS Lett. 1993; 323: 211-4.
152. Llovera M, García-Martínez C, Agell N, Marzábal M, López-Soriano FJ, Argilés JM. Ubiquitin gene expression is increased in skeletal muscle of tumour-bearing rats. FEBS Lett. 1994; 338: 311-8.
153. Temparis S, Asensi M, Taillandier D, Aurousseau E, Larbaud D, Obled A, et al. Increased ATP-ubiquitin-dependent proteolysis in skeletal muscles of tumor-bearing rats. Cancer Res. 1994; 54: 5568-73.
154. Baracos VE, DeVivo C, Hoyle DH, Goldberg AL. Activation of the ATP-ubiquitin-proteasome pathway in skeletal muscle of cachectic rats bearing a hepatoma. Am J Physiol. 1995; 268: E996-1006.
155. Lorite MJ, Thompson MG, Drake JL, Carling G, Tisdale MJ. Mechanism of muscle protein degradation induced by a cancer cachectic factor. Br J Cancer. 1998; 78: 850-6.
156. Solomon V, Baracos V, Sarraf P, Goldberg AL. Rates of ubiquitin conjugation increase when muscles atrophy, largely through activation of the N-end rule pathway. Proc Natl Acad Sci U S A. 1998; 95: 12602-7.
157. Siddiqui RA, Hassan S, Harvey KA, Rasool T, Das T, Mukerji P, et al. Attenuation of proteolysis and muscle wasting by curcumin c3 complex in MAC16 colon tumour-bearing mice. Br J Nutr. 2009; 102: 967-75.
158. Asp ML, Tian M, Wendel AA, Belury MA. Evidence for the contribution of insulin resistance to the development of cachexia in tumor-bearing mice. Int J Cancer. 2010; 126: 756-63.
159. Wing SS, Haas AL, Goldberg AL. Increase in ubiquitin-protein conjugates concomitant with the increase in proteolysis in rat skeletal muscle during starvation and atrophy denervation. Biochem J. 1995; 307: 639-45.
160. Moresi V, Williams AH, Meadows E, Flynn JM, Potthoff MJ, McAnally J, et al. Myogenin and class II HDACs control neurogenic muscle atrophy by inducing E3 ubiquitin ligases. Cell. 2010; 143: 35-45.
161. Hobler SC, Williams A, Fischer D, Wang JJ, Sun X, Fischer JE, et al. Activity and expression of the 20 S proteasome are increased in skeletal muscle during sepsis. Am J Physiol. 1999; 277: R434-40.
162. Wray CJ, Mammen JM, Hershko DD, Hasselgren PO. Sepsis upregulates the gene expression of multiple ubiquitin ligases in skeletal muscle. Int J Biochem Cell Biol. 2003; 35: 698-705.
163. Granado M, Priego T, Martín AI, Villanúa MA, López-Calderón A. Ghrelin receptor agonist GHRP-2 prevents arthritis-induced increase in E3 ubiquitin-ligating enzymes MuRF1 and MAFbx gene expression in skeletal muscle. Am J Physiol Endocrinol Metab. 2005; 289: E1007-14.
164. Doucet M, Russell AP, Léger B, Debigaré R, Joanisse DR, Caron MA, et al. Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2007; 176: 261-9.
165. Vary TC, Frost RA, Lang CH. Acute alcohol intoxication increases atrogin-1 and MuRF1 mRNA without increasing proteolysis in skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2008; 294: R1777-89.
166. Otis JS, Ashikhmin YI, Brown LA, Guidot DM. Effect of HIV-1-related protein expression on cardiac and skeletal muscles from transgenic rats. AIDS Res Ther. 2008; 5: 8.
167. Zeman RJ, Zhao J, Zhang Y, Zhao W, Wen X, Wu Y, et al. Differential skeletal muscle gene expression after upper or lower motor neuron transection. Pflugers Arch. 2009; 458: 525-35.
168. Klionsky DJ. Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol. 2007; 8: 931-7.
169. Levine B, Yuan J. Autophagy in cell death: an innocent convict? J Clin Invest. 2005; 115: 2679-88.
170. Yang Z, Klionsky DJ. Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol. 2010; 22: 124-31.
171. Nishino I. Autophagic vacuolar myopathies. Curr Neurol Neurosci Rep. 2003; 3: 64-9.
172. Raben N, Roberts A, Plotz PH. Role of autophagy in the pathogenesis of Pompe disease. Acta Myol. 2007; 26: 45-8.
173. Suzuki T, Nakagawa M, Yoshikawa A, Sasagawa N, Yoshimori T, Ohsumi Y, et al. The first molecular evidence that autophagy relates rimmed vacuole formation in chloroquine myopathy. J Biochem. 2002; 131: 647-51.
174. Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, et al. Autophagy is required to maintain muscle mass. Cell Metab. 2009; 10: 507-15.
175. Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y. In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell. 2004; 15: 1101-11.
176. Aucello M, Dobrowolny G, Musarò A. Localized accumulation of oxidative stress causes muscle atrophy through activation of an autophagic pathway. Autophagy. 2009; 5: 527-9.
177. Schiaffino S, Hanzlíková V. Studies on the effect of denervation in developing muscle. II. The lysosomal system. J Ultrastruct Res. 1972; 39: 1-14.
178. Sandri M. Autophagy in health and disease. 3. Involvement of autophagy in muscle atrophy. Am J Physiol Cell Physiol. 2010; 298: C1291-7.
179. Rossi S, Stoppani E, Martinet W, Bonetto A, Costelli P, Giuliani R, et al. The cytosolic sialidase Neu2 is degraded by autophagy during myoblast atrophy. Biochim Biophys Acta. 2009; 1790: 817-28.
180. Sandri M. Autophagy in skeletal muscle. FEBS Lett. 2010; 584: 1411-6.
181. Hengartner MO. The biochemistry of apoptosis. Nature. 2000; 407: 770-6.
182. Hotchkiss RS, Strasser A, McDunn JE, Swanson PE. Cell death. N Engl J Med. 2009; 361: 1570-83.
183. Dirks A, Leeuwenburgh C. Apoptosis in skeletal muscle with aging. Am J Physiol Regul Integr Comp Physiol. 2002; 282: R519-27.
184. Dirks-Naylor AJ, Lennon-Edwards S. Cellular and molecular mechanisms of apoptosis in age-related muscle atrophy. Curr Aging Sci. 2011.
185. Alway SE, Siu PM. Nuclear apoptosis contributes to sarcopenia. Exerc Sport Sci Rev. 2008; 36: 51-7.
186. Belizário JE, Lorite MJ, Tisdale MJ. Cleavage of caspases-1, -3, -6, -8 and -9 substrates by proteases in skeletal muscles from mice undergoing cancer cachexia. Br J Cancer. 2001; 84: 1135-40.
187. Vescovo G, Dalla Libera L. Skeletal muscle apoptosis in experimental heart failure: the only link between inflammation and skeletal muscle wastage? Curr Opin Clin Nutr Metab Care. 2006; 9: 416-22.
188. Siu PM, Alway SE. Response and adaptation of skeletal muscle to denervation stress: the role of apoptosis in muscle loss. Front Biosci. 2009; 14: 432-52.
189. Sandri M, Carraro U, Podhorska-Okolov M, Rizzi C, Arslan P, Monti D, et al. Apoptosis, DNA damage and ubiquitin expression in normal and mdx muscle fibers after exercise. FEBS Lett. 1995; 373: 291-5.
190. Hasselgren PO, Menconi MJ, Fareed MU, Yang H, Wei W, Evenson A. Novel aspects on the regulation of muscle wasting in sepsis. Int J Biochem Cell Biol. 2005; 37: 2156-68.
191. Allen DL, Linderman JK, Roy RR, Bigbee AJ, Grindeland RE, Mukku V, et al. Apoptosis: a mechanism contributing to remodeling of skeletal muscle in response to hindlimb unweighting. Am J Physiol. 1997; 273: C579-87.
192. Siu PM. Muscle apoptotic response to denervation, disuse, and aging. Med Sci Sports Exerc. 2009; 41: 1876-86.
193. Yasuhara S, Perez ME, Kanakubo E, Yasuhara Y, Shin YS, Kaneki M, et al. Skeletal muscle apoptosis after burns is associated with activation of proapoptotic signals. Am J Physiol Endocrinol Metab. 2000; 279: E1114-21.
194. Conraads VM, Hoymans VY, Vermeulen T, Beckers P, Possemiers N, Maeseneer MD, et al. Exercise capacity in chronic heart failure patients is related to active gene transcription in skeletal muscle and not apoptosis. Eur J Cardiovasc Prev Rehabil. 2009; 16: 325-32.
195. Du J, Wang X, Miereles C, Bailey JL, Debigare R, Zheng B, et al. Activation of caspase-3 is an initial step triggering accelerated muscle proteolysis in catabolic conditions. J Clin Invest. 2004; 113: 115-23.
196. Pistilli EE, Jackson JR, Alway SE. Death receptor-associated pro-apoptotic signaling in aged skeletal muscle. Apoptosis. 2006; 11: 2115-26.
197. von Haehling S, Lainscak M, Springer J, Anker SD. Cardiac cachexia: a systematic overview. Pharmacol Ther. 2009; 121: 227-52.
198. Rüegg MA, Glass DJ. Molecular mechanisms and treatment options for muscle wasting diseases. Annu Rev Pharmacol Toxicol. 2011; 51: 373-95.
199. Alvers AL, Fishwick LK, Wood MS, Hu D, Chung HS, Dunn WA, et al. Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae. Aging Cell. 2009; 8: 353-69.
200. Avruch J, Long X, Ortiz-Vega S, Rapley J, Papageorgiou A, Dai N. Amino acid regulation of TOR complex 1. Am J Physiol Endocrinol Metab. 2009; 296: E592-602.
201. Schieke SM, Phillips D, McCoy JP, Aponte AM, Shen RF, Balaban RS, et al. The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J Biol Chem. 2006; 281: 27643-52.
202. Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature. 2007; 450: 736-40.
203. D'Antona G, Ragni M, Cardile A, Tedesco L, Dossena M, Bruttini F, et al. Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metab. 2010; 12: 362-72.
204. Eley HL, Russell ST, Tisdale MJ. Effect of branched-chain amino acids on muscle atrophy in cancer cachexia. Biochem J. 2007; 407: 113-20.
205. Herningtyas EH, Okimura Y, Handayaningsih AE, Yamamoto D, Maki T, Iida K, et al. Branched-chain amino acids and arginine suppress MaFbx/atrogin-1 mRNA expression via mTOR pathway in C2C12 cell line. Biochim Biophys Acta. 2008; 1780: 1115-20.
206. Colomer R, Moreno-Nogueira JM, García-Luna PP, García-Peris P, García-de-Lorenzo A, Zarazaga A, et al. N-3 fatty acids, cancer and cachexia: a systematic review of the literature. Br J Nutr. 2007; 97: 823-31.
207. van Norren K, Kegler D, Argilés JM, Luiking Y, Gorselink M, Laviano A, et al. Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice. Br J Cancer. 2009; 100: 713-22.
208. Palus S, Schur R, Akashi YJ, Bockmeyer B, Datta R, Halem H, et al. Ghrelin and Its Analogues, BIM-28131 and BIM-28125, Improve Body Weight and Regulate the Expression of MuRF-1 and MAFbx in a Rat Heart Failure Model. PLoS One. 2011; 6: e26865.
209. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999; 402: 656-60.
210. Sanders PM, Russell ST, Tisdale MJ. Angiotensin II directly induces muscle protein catabolism through the ubiquitin-proteasome proteolytic pathway and may play a role in cancer cachexia. Br J Cancer. 2005; 93: 425-34.
211. Anker SD, Negassa A, Coats AJ, Afzal R, Poole-Wilson PA, Cohn JN, et al. Prognostic importance of weight loss in chronic heart failure and the effect of treatment with angiotensin-converting-enzyme inhibitors: an observational study. Lancet. 2003; 361: 1077-83.
212. Anker SD, Chua TP, Ponikowski P, Harrington D, Swan JW, Kox WJ, et al. Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia. Circulation. 1997; 96: 526-34.
213. Malkin CJ, Pugh PJ, West JN, van Beek EJ, Jones TH, Channer KS. Testosterone therapy in men with moderate severity heart failure: a double-blind randomized placebo controlled trial. Eur Heart J. 2006; 27: 57-64.
214. Bhasin S, Jasuja R. Selective androgen receptor modulators as function promoting therapies. Curr Opin Clin Nutr Metab Care. 2009; 12: 232-40.
215. Zilbermint MF, Dobs AS. Nonsteroidal selective androgen receptor modulator Ostarine in cancer cachexia. Future Oncol. 2009; 5: 1211-20.
216. Dalton JT, Barnette KG, Bohl CE, Hancock ML, Rodriguez D, Dodson ST, et al. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J Cachexia Sarcopenia Muscle. 2011; 2: 153-61.
217. Anker SD, Volterrani M, Pflaum CD, Strasburger CJ, Osterziel KJ, Doehner W, et al. Acquired growth hormone resistance in patients with chronic heart failure: implications for therapy with growth hormone. J Am Coll Cardiol. 2001; 38: 443-52.
218. Schmidt K, von Haehling S, Doehner W, Palus S, Anker SD, Springer J. IGF-1 treatment reduces weight loss and improves outcome in a rat model of cancer cachexia. J Cachexia Sarcopenia Muscle. 2011; 2: 105-9.
219. Ryall JG, Lynch GS. The potential and the pitfalls of beta-adrenoceptor agonists for the management of skeletal muscle wasting. Pharmacol Ther. 2008; 120: 219-32.
220. Kenley RA, Denissenko MF, Mullin RJ, Story J, Ekblom J. Formoterol fumarate and roxithromycin effects on muscle mass in an animal model of cancer cachexia. Oncol Rep. 2008; 19: 1113-21.
221. Mann DL, McMurray JJ, Packer M, Swedberg K, Borer JS, Colucci WS, et al. Targeted anticytokine therapy in patients with chronic heart failure: results of the Randomized Etanercept Worldwide Evaluation (RENEWAL). Circulation. 2004; 109: 1594-602.
222. Chung ES, Packer M, Lo KH, Fasanmade AA, Willerson JT, Investigators A-TTACHF. Randomized, double-blind, placebo-controlled, pilot trial of infliximab, a chimeric monoclonal antibody to tumor necrosis factor-alpha, in patients with moderate-to-severe heart failure: results of the anti-TNF Therapy Against Congestive Heart Failure (ATTACH) trial. Circulation. 2003; 107: 3133-40.
223. Mantovani G, Macciò A, Madeddu C, Serpe R, Antoni G, Massa E, et al. Phase II nonrandomized study of the efficacy and safety of COX-2 inhibitor celecoxib on patients with cancer cachexia. J Mol Med (Berl). 2010; 88: 85-92.
224. Tavazzi L, Maggioni AP, Marchioli R, Barlera S, Franzosi MG, Latini R, et al. Effect of n-3 polyunsaturated fatty acids in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008; 372: 1223-30.
225. Sharma R, von Haehling S, Rauchhaus M, Bolger AP, Genth-Zotz S, Doehner W, et al. Whole blood endotoxin responsiveness in patients with chronic heart failure: the importance of serum lipoproteins. Eur J Heart Fail. 2005; 7: 479-84.
226. Rauchhaus M, Doehner W, Francis DP, Davos C, Kemp M, Liebenthal C, et al. Plasma cytokine parameters and mortality in patients with chronic heart failure. Circulation. 2000; 102: 3060-7.
227. Doehner W, Rauchhaus M, Ponikowski P, Godsland IF, von Haehling S, Okonko DO, et al. Impaired insulin sensitivity as an independent risk factor for mortality in patients with stable chronic heart failure. J Am Coll Cardiol. 2005; 46: 1019-26.
228. van Gaal LF, Mertens IL, De Block CE. Mechanisms linking obesity with cardiovascular disease. Nature. 2006; 444: 875-80.
229. Kistorp C, Faber J, Galatius S, Gustafsson F, Frystyk J, Flyvbjerg A, et al. Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation. 2005; 112: 1756-62.
230. Cui J, Panse S, Falkner B. The role of adiponectin in metabolic and vascular disease: a review. Clin Nephrol. 2011; 75: 26-33.
231. van Berendoncks AM, Garnier A, Beckers P, Hoymans VY, Possemiers N, Fortin D, et al. Functional adiponectin resistance at the level of the skeletal muscle in mild to moderate chronic heart failure. Circ Heart Fail. 2010; 3: 185-94.
232. van Berendoncks AM, Garnier A, Beckers P, Hoymans VY, Possemiers N, Fortin D, et al. Exercise training reverses adiponectin resistance in skeletal muscle of patients with chronic heart failure. Heart. 2011; 97: 1403-9.
233. Siew ED, Ikizler TA. Insulin resistance and protein energy metabolism in patients with advanced chronic kidney disease. Semin Dial. 2010; 23: 378-82.
234. Castillero E, Nieto-Bona MP, Fernández-Galaz C, Martín AI, López-Menduiña M, Granado M, et al. Fenofibrate, a PPAR{alpha} agonist, decreases atrogenes and myostatin expression and improves arthritis-induced skeletal muscle atrophy. Am J Physiol Endocrinol Metab. 2011; 300: E790-9.
235. Tawa NE, Odessey R, Goldberg AL. Inhibitors of the proteasome reduce the accelerated proteolysis in atrophying rat skeletal muscles. J Clin Invest. 1997; 100: 197-203.
236. Fischer D, Gang G, Pritts T, Hasselgren PO. Sepsis-induced muscle proteolysis is prevented by a proteasome inhibitor in vivo. Biochem Biophys Res Commun. 2000; 270: 215-21.
237. Jamart C, Raymackers JM, Li An G, Deldicque L, Francaux M. Prevention of muscle disuse atrophy by MG132 proteasome inhibitor. Muscle Nerve. 2011; 43: 708-16.
238. Caron AZ, Haroun S, Leblanc E, Trensz F, Guindi C, Amrani A, et al. The proteasome inhibitor MG132 reduces immobilization-induced skeletal muscle atrophy in mice. BMC Musculoskelet Disord. 2011; 12: 185.
239. Carmignac V, Quéré R, Durbeej M. Proteasome inhibition improves the muscle of laminin α2 chain-deficient mice. Hum Mol Genet. 2011; 20: 541-52.
240. Beehler BC, Sleph PG, Benmassaoud L, Grover GJ. Reduction of skeletal muscle atrophy by a proteasome inhibitor in a rat model of denervation. Exp Biol Med (Maywood). 2006; 231: 335-41.
241. Kwon DY, Motley WW, Fischbeck KH, Burnett BG. Increasing expression and decreasing degradation of SMN ameliorate the spinal muscular atrophy phenotype in mice. Hum Mol Genet. 2011; 20: 3667-77.
242. Madeddu C, Mantovani G. An update on promising agents for the treatment of cancer cachexia. Curr Opin Support Palliat Care. 2009; 3: 258-62.
243. Conraads VM, Beckers P, Bosmans J, De Clerck LS, Stevens WJ, Vrints CJ, et al. Combined endurance/resistance training reduces plasma TNF-alpha receptor levels in patients with chronic heart failure and coronary artery disease. Eur Heart J. 2002; 23: 1854-60.
244. Gielen S, Adams V, Möbius-Winkler S, Linke A, Erbs S, Yu J, et al. Anti-inflammatory effects of exercise training in the skeletal muscle of patients with chronic heart failure. J Am Coll Cardiol. 2003; 42: 861-8.
245. Linke A, Adams V, Schulze PC, Erbs S, Gielen S, Fiehn E, et al. Antioxidative effects of exercise training in patients with chronic heart failure: increase in radical scavenger enzyme activity in skeletal muscle. Circulation. 2005; 111: 1763-70.
246. Adams V, Mangner N, Gasch A, Krohne C, Gielen S, Hirner S, et al. Induction of MuRF1 is essential for TNF-alpha-induced loss of muscle function in mice. J Mol Biol. 2008; 384: 48-59.
247. Heineke J, Auger-Messier M, Xu J, Sargent M, York A, Welle S, et al. Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure. Circulation. 2010; 121: 419-25.
248. Lenk K, Schur R, Linke A, Erbs S, Matsumoto Y, Adams V, et al. Impact of exercise training on myostatin expression in the myocardium and skeletal muscle in a chronic heart failure model. Eur J Heart Fail. 2009; 11: 342-8.
249. Lenk K, Erbs S, Höllriege R, Beck E, Linke A, Gielen S, Möbius Winkler S, Sandri M, Hambrecht R, Schuler G, Adams V. Exercise training leads to a reduction of elevated myostatin levels in patients with chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2011; 19: 404-11.
250. Penna F, Busquets S, Pin F, Toledo M, Baccino FM, López-Soriano FJ, et al. Combined approach to counteract experimental cancer cachexia: eicosapentaenoic acid and training exercise. J Cachexia Sarcopenia Muscle. 2011; 2: 95-104.
251. von Haehling S, Morley JE, Coats AJ, Anker SD. Ethical guidelines for authorship and publishing in the Journal of Cachexia, Sarcopenia and Muscle. J Cachexia Sarcopenia Muscle. 2010; 1: 7-8.