The muscle-hypertrophic effect of clenbuterol is additive to the hypertrophic effect of myostatin suppression

Muscle and Nerve

Volumn 43, Issue 5, 2011, Pages 700-707

  Kim, Kyung Ho ^a   Kim, Yong Soo ^a   Yang, Jinzeng ^a  

^a UNIVERSITY OF HAWAII   (United States)

Author keywords

agonist; Clenbuterol; Mtor pathway; Muscle growth; Myostatin; Myostatin prodomain

Indexed keywords

CLENBUTEROL; DRINKING WATER; INITIATION FACTOR 4E BINDING PROTEIN 1; MAMMALIAN TARGET OF RAPAMYCIN; MYOSTATIN; PROTEIN KINASE B; S6 KINASE;

ARTICLE; BIOSYNTHESIS; BODY MASS; CONTROLLED STUDY; DRUG EFFECT; FEMALE; GENOTYPE; HETEROZYGOSITY; MALE; MOUSE; MUSCLE GROWTH; MUSCLE HYPERTROPHY; MUSCLE MASS; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; TRANSGENIC MOUSE; WILD TYPE;

ANABOLIC AGENTS; ANIMALS; CLENBUTEROL; DRUG SYNERGISM; FEMALE; HYPERTROPHY; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MUSCLE, SKELETAL; MYOSTATIN; RANDOM ALLOCATION;

EID: 79955562785     PISSN: 0148639X     EISSN: 10974598     Source Type: Journal    
DOI: 10.1002/mus.21950     Document Type: Article

References (52)

1. Lynch GS, Ryall JG. Role of beta-adrenoceptor signaling in skeletal muscle: implications for muscle wasting and disease. Physiol Rev 2008;88:729-767.
2. Lee SJ. Regulation of muscle mass by myostatin. Annu Rev Cell Dev Biol 2004;20:61-86.
3. Carter WJ, Dang AQ, Faas FH, Lynch ME. Effects of clenbuterol on skeletal muscle mass, body composition, and recovery from surgical stress in senescent rats. Metabolism 1991;40:855-860.
4. Fowler EG, Graves MC, Wetzel GT, Spencer MJ. Pilot trial of albuterol in Duchenne and Becker muscular dystrophy. Neurology 2004;62: 1006-1008.
5. Kissel JT, McDermott MP, Mendell JR, King WM, Pandya S, Griggs RC, et al. Randomized, double-blind, placebo-controlled trial of albuterol in facioscapulohumeral dystrophy. Neurology 2001;57:1434-1440.
6. Lynch GS, Hinkle RT, Chamberlain JS, Brooks SV, Faulkner JA. Force and power output of fast and slow skeletal muscles from mdx mice 6-28 months old. J Physiol 2001;535:591-600.
7. Maltin CA, Delday MI, Watson JS, Heys SD, Nevison IM, Ritchie IK, et al. Clenbuterol, a beta-adrenoceptor agonist, increases relative muscle strength in orthopaedic patients. Clin Sci (Lond) 1993;84: 651-654.
8. Bogdanovich S, Perkins KJ, Krag TO, Whittemore LA, Khurana TS. Myostatin propeptide-mediated amelioration of dystrophic pathophysiology. FASEB J 2005;19:543-549.
9. Jespersen J, Kjaer M, Schjerling P. The possible role of myostatin in skeletal muscle atrophy and cachexia. Scand J Med Sci Sports 2006; 16:74-82.
10. Li ZF, Shelton GD, Engvall E. Elimination of myostatin does not combat muscular dystrophy in dy mice but increases postnatal lethality. Am J Pathol 2005;166:491-497.
11. Wagner KR, Liu X, Chang X, Allen RE. Muscle regeneration in the prolonged absence of myostatin. Proc Natl Acad Sci USA 2005;102: 2519-2524.
12. Wagner KR, McPherron AC, Winik N, Lee SJ. Loss of myostatin attenuates severity of muscular dystrophy in mdx mice. Ann Neurol 2002; 52:832-836.
13. Van der Kooi EL, Vogels OJ, van Asseldonk RJ, Lindeman E, Hendriks JC, Wohlgemuth M, et al. Strength training and albuterol in facioscapulohumeral muscular dystrophy. Neurology 2004;63:702-708.
14. Hill JJ, Davies MV, Pearson AA, Wang JH, Hewick RM, Wolfman NM, et al. The myostatin propeptide and the follistatin-related gene are inhibitory binding proteins of myostatin in normal serum. J Biol Chem 2002;277:40735-40741.
15. Thies RS, Chen T, Davies MV, Tomkinson KN, Pearson AA, Shakey QA, et al. GDF-8 propeptide binds to GDF-8 and antagonizes biological activity by inhibiting GDF-8 receptor binding. Growth Factors 2001; 18:251-259.
16. Lee SJ, McPherron AC. Regulation of myostatin activity and muscle growth. Proc Natl Acad Sci USA 2001;98:9306-9311.
17. Yang J, Ratovitski T, Brady JP, Solomon MB, Wells KD, Wall RJ. Expression of myostatin pro domain results in muscular transgenic mice. Mol Reprod Dev 2001;60:351-361.
18. Lee SJ, Reed LA, Davies MV, Girgenrath S, Goad ME, Tomkinson KN, et al. Regulation of muscle growth by multiple ligands signaling through activin type II receptors. Proc Natl Acad Sci USA 2005;102: 18117-18122.
19. Rebbapragada A, Benchabane H, Wrana JL, Celeste AJ, Attisano L. Myostatin signals through a transforming growth factor beta-like signaling pathway to block adipogenesis. Mol Cell Biol 2003;23:7230-7242.
20. Bogdanovich S, Krag TO, Barton ER, Morris LD, Whittemore LA, Ahima RS, et al. Functional improvement of dystrophic muscle by myostatin blockade. Nature 2002;420:418-421.
21. Langley B, Thomas M, Bishop A, Sharma M, Gilmour S, Kambadur R. Myostatin inhibits myoblast differentiation by down-regulating MyoD expression. J Biol Chem 2002;277:49831-49840.
22. Zhu X, Topouzis S, Liang LF, Stotish RL. Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism. Cytokine 2004;26:262-272.
23. Sartori R, Milan G, Patron M, Mammucari C, Blaauw B, Abraham R, et al. Smad2 and 3 transcription factors control muscle mass in adulthood. Am J Physiol Cell Physiol 2009;296:C1248-C1257.
24. 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-C1270.
25. 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;3:1014-1019.
26. Drummond MJ, Dreyer HC, Fry CS, Glynn EL, Rasmussen BB. Nutritional and contractile regulation of human skeletal muscle protein synthesis and mTORC1 signaling. J Appl Physiol 2009;106: 1374-1384.
27. Proud CG. Signalling to translation: how signal transduction pathways control the protein synthetic machinery. Biochem J 2007;403: 217-234.
28. Wang X, Proud CG. The mTOR pathway in the control of protein synthesis. Physiology (Bethesda) 2006;21:362-369.
29. 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;150:286-294.
30. Welle S, Bhatt K, Pinkert CA. Myofibrillar protein synthesis in myostatin- deficient mice. Am J Physiol Endocrinol Metab 2006;290: E409-415.
31. Welle S, Burgess K, Mehta S. Stimulation of skeletal muscle myofibrillar protein synthesis, p70 S6 kinase phosphorylation, and ribosomal protein S6 phosphorylation by inhibition of myostatin in mature mice. Am J Physiol Endocrinol Metab 2009;296:E567-E572.
32. Kim YS, Sainz RD. Beta-adrenergic agonists and hypertrophy of skeletal muscles. Life Sci 1992;50:397-407.
33. Mersmann HJ. Overview of the effects of beta-adrenergic receptor agonists on animal growth including mechanisms of action. J Anim Sci 1998;76:160-172.
34. Maltin CA, Hay SM, McMillan DN, Delday MI. Tissue specific responses to clenbuterol; temporal changes in protein metabolism of striated muscle and visceral tissues from rats. Growth Regul 1992;2:161-166.
35. McElligott MA, Barreto A Jr, Chaung LY. Effect of continuous and intermittent clenbuterol feeding on rat growth rate and muscle. Comp Biochem Physiol C 1989;92:135-138.
36. Pierce KL, Premont RT, Lefkowitz RJ. Seven-transmembrane receptors. Nat Rev Mol Cell Biol 2002;3:639-650.
37. Hinkle RT, Hodge KM, Cody DB, Sheldon RJ, Kobilka BK, Isfort RJ. Skeletal muscle hypertrophy and anti-atrophy effects of clenbuterol are mediated by the beta2-adrenergic receptor. Muscle Nerve 2002; 25:729-734.
38. Kline WO, Panaro FJ, Yang H, Bodine SC. Rapamycin inhibits the growth and muscle-sparing effects of clenbuterol. J Appl Physiol 2007;102:740-747.
39. Sneddon AA, Delday MI, Steven J, Maltin CA. Elevated IGF-II mRNA and phosphorylation of 4E-BP1 and p70(S6k) in muscle showing clenbuterol-induced anabolism. Am J Physiol Endocrinol Metab 2001;281:E676-E682.
40. Lynch GS, Hayes A, Campbell SP, Williams DA. Effects of beta 2-agonist administration and exercise on contractile activation of skeletal muscle fibers. J Appl Physiol 1996;81:1610-1618.
41. Munro HN. The determination of nucleic acids. Methods Biochem Anal 1966;14:113-176.
42. Brunk CF, Jones KC, James TW. Assay for nanogram quantities of DNA in cellular homogenates. Anal Biochem 1979;92:497-500.
43. Dreyer HC, Fujita S, Cadenas JG, Chinkes DL, Volpi E, Rasmussen BB. Resistance exercise increases AMPK activity and reduces 4E-BP1 phosphorylation and protein synthesis in human skeletal muscle. J Physiol 2006;576:613-624.
44. Sarbassov DD, Ali SM, Sabatini DM. Growing roles for the mTOR pathway. Curr Opin Cell Biol 2005;17:596-603.
45. Pallafacchina G, Calabria E, Serrano AL, Kalhovde JM, Schiaffino S. A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification. Proc Natl Acad Sci USA 2002;99:9213-9218.
46. Dreyer HC, Drummond MJ, Pennings B, Fujita S, Glynn EL, Chinkes DL, et al. Leucine-enriched essential amino acid and carbohydrate ingestion following resistance exercise enhances mTOR signaling and protein synthesis in human muscle. Am J Physiol Endocrinol Metab 2008;294:E392-E400.
47. Drummond MJ, Dreyer HC, Pennings B, Fry CS, Dhanani S, Dillon EL, et al. Skeletal muscle protein anabolic response to resistance exercise and essential amino acids is delayed with aging. J Appl Physiol 2008;104:1452-1461.
48. Fujita S, Dreyer HC, Drummond MJ, Glynn EL, Cadenas JG, Yoshizawa F, et al. Nutrient signalling in the regulation of human muscle protein synthesis. J Physiol 2007;582:813-823.
49. Hornberger TA, Hunter RB, Kandarian SC, Esser KA. Regulation of translation factors during hindlimb unloading and denervation of skeletal muscle in rats. Am J Physiol Cell Physiol 2001;281: C179-C187.
50. Harcourt LJ, Schertzer JD, Ryall JG, Lynch GS. Low dose formoterol administration improves muscle function in dystrophic mdx mice without increasing fatigue. Neuromuscul Disord 2007;17:47-55.
51. Ryall JG, Sillence MN, Lynch GS. Systemic administration of beta2- adrenoceptor agonists, formoterol and salmeterol, elicit skeletal muscle hypertrophy in rats at micromolar doses. Br J Pharmacol 2006; 147:587-595.
52. Busquets S, Figueras MT, Fuster G, Almendro V, Moore-Carrasco R, Ametller E, et al. Anticachectic effects of formoterol: a drug for potential treatment of muscle wasting. Cancer Res 2004;64: 6725-6731.