growth/differentiation factor-8; myostatin (GDF-8, MSTN)
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Function
- negative regulator of skeletal muscle growth
- may increase tendon strength & flexiblity[6]
- binds to extracellular activin receptor 2B (ACTR2B) to induce intracellular activation of SMAD proteins, SMAD2 & SMAD3
- propeptide of GDF8 binds to the mature homodimer to form a latent myostatin complex, thus regulates GDF8 activity by preventing the homodimer from binding to its target receptors
- myostatin inhibits progression of muscle stem cells through the cell cycle[5]
- effect appears to be specific for type 2 muscle fiber stem cells
- upregulates CDKN1A (p21WAF1)
- supresses CDK2 expression
- inhibits phosphorylation of Rb protein
- may directly inhibit myogenic regulatory factor expression
Structure
- homodimer, disulfide-linked
- 26-kD mature glycoprotein
- 89% sequence homology with GDF11
Compartment
Expression
- expressed uniquely in human skeletal muscle
- secreted into the plasma
- occurs in both type 1 & type 2 muscle fibers
- myostatin plasma levels decline with age in mice, rats, horses & sheep[7]
Pathology
- myostatin deficiency[3] is associated with
- skeletal muscle hypertrophy
- increased metabolic rate
- enhanced muscle repair, rejuvenation
- diminished body fat
- no effect on cardiac muscle
- no known adverse effects
age-related increases in serum myostatin inversely correlate with muscle mass, suggesting that myostatin may contribute to sarcopenia[5]
- evidence of age-related loss of muscle mass in myostatin- null mutant mice, suggest myostatin is not the only mediator of sarcopenia
- myostatin plasma levels decline with age in mice, rats, horses & sheep[7]
- in patients with stable ischemic heart disease, higher GDF11/GDF8 (myostatin) levels are associated with lower risk of cardiovascular events & death[8]
Comparative biology
- in mice, recombinant myostatin enhances repair & regeneration of both muscle & bone after musculoskeletal injury[9]
More general terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/O14793.html
- ↑ GeneReviews https://www.genecards.org/cgi-bin/carddisp.pl?gene=GDF8
- ↑ 3.0 3.1 Rare condition gives toddler super strength Associated Press, May 30, 2007 http://www.netscape.com/viewstory/2007/06/02/rare-condition-gives-toddler-super-strength/?url=http%3A%2F%2Fwww.ctv.ca%2Fservlet%2FArticleNews%2Fstory%2FCTVNews%2F20070530%2Fstrong_toddler_070530%2F20070530%3Fhub%3DHealth&frame=true
- ↑ Saunders MA, Good JM, Lawrence EC, Ferrell RE, Li WH, Nachman MW. Human adaptive evolution at Myostatin (GDF8), a regulator of muscle growth. Am J Hum Genet. 2006 Dec;79(6):1089-97. Epub 2006 Oct 10. PMID: https://www.ncbi.nlm.nih.gov/pubmed/17186467
- ↑ 5.0 5.1 5.2 McKay BR et al Myostatin is associated with age-related human muscle stem cell dysfunction FASEB J March 7, 2012 PMID: https://www.ncbi.nlm.nih.gov/pubmed/22403007
- ↑ 6.0 6.1 6.2 No Authors Myostatin inhibitors may make injuries more likely Drug Trial News, January 23, 200 http://www.news-medical.net/news/2008/01/23/34633.aspx?page=2
- ↑ 7.0 7.1 7.2 Poggioli T, Vujic A, Yang P et al Circulating Growth Differentiation Factor 11/8 Levels Decline with Age. Circ Res.. Oct 21, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26489925 <Internet> http://circres.ahajournals.org/content/early/2015/10/21/CIRCRESAHA.115.307521.abstract
- ↑ 8.0 8.1 Olson KA, Beatty AL, Heidecker B et al Association of growth differentiation factor 11/8, putative anti-ageing factor, with cardiovascular outcomes & overall mortality in humans: analysis of the Heart and Soul and HUNT3 cohorts. European Heart Journal. Aug 20, 2015 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26294790 <Internet> http://eurheartj.oxfordjournals.org/content/early/2015/08/20/eurheartj.ehv385
- ↑ 9.0 9.1 Hamrick MW, Arounleut P, Kellum E et al Recombinant myostatin (GDF-8) propeptide enhances the repair and regeneration of both muscle and bone in a model of deep penetrant musculoskeletal injury J Trauma. 2010 Sep;69(3):579-83. doi:http://dx.doi.org/ 10.1097/TA.0b013e3181c451f4. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20173658 Free PMC Article