Myostatin Inhibits IGF-I-Induced Myotube Hypertrophy through Akt
Open accessAbstract
Myostatin is a highly conserved negative regulator of skeletal muscle growth. Loss of functional myostatin in cattle, mice, sheep, dogs, and humans results in increased muscle mass. The molecular mechanisms responsible for this increase in muscle growth are not fully understood. Previously, we have reported that phenylephrine-induced cardiac muscle growth and Akt activation are enhanced in myostatin knockout mice compared with controls. Here we report that skeletal muscle from myostatin knockout mice show increased Akt protein expression and overall activity at baseline secondary to an increase in Akt mRNA. We examined the functional role of myostatin modulation of Akt in C2C12 myotubes, a well-established in vitro model of skeletal muscle hypertrophy. Adenoviral overexpression of myostatin attenuated the insulin-like growth factor-I (IGF-I)-mediated increase in myotube diameter, as well as IGF-I-stimulated Akt phosphorylation. Inhibition of myostatin by overexpression of the NH(2)-terminal portion of myostatin was sufficient to increase myotube diameter and Akt phosphorylation. Coexpression of myostatin and constitutively active Akt (myr-Akt) restored the increase in myotube diameter. Conversely, expression of dominant negative Akt (dn-Akt) with the inhibitory myostatin propeptide blocked the increase in myotube diameter. Of note, ribosomal protein S6 phosphorylation and atrogin-1/muscle atrophy F box mRNA were increased in skeletal muscle from myostain knockout mice. Togeth…
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Upon binding to its receptor, the activin receptor type II A/B, myostatin activates catabolic pathways via phosphorylation of Smad2/3 and simultaneously inhibits anabolic pathways.
“Upon binding to its receptor, the activin receptor type II A/B, it activates catabolic pathways via the phosphorylation of downstream effectors Smad2/3 and simultaneously inhibits anabolic pathways [175].”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [175]
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- Authors
- Morissette, M. R., Cook, S. A., Buranasombati, C., Rosenberg, M. A., & Rosenzweig, A.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Hammersmith Hospital (GB)
- Corresponding author
- Rosenzweig, Anthony
- Venue
- American Journal of Physiology-Cell Physiology
- Publisher
- American Physiological Society
- Published
- 2009-11
- Volume
- 297
- Issue
- 5
- Pages
- 1124-1132
- ISSN
- 0363-6143 (ISSN-L)
- 1522-1563
- PMC
- PMC2777401
- OpenAlex
- W2066056709
- Cited by
- 231
- References
- 11
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 12 · 2023: 12 · 2022: 15 · 2021: 13 · 2020: 12 · 2019: 10 · 2018: 18 · 2017: 9 · 2016: 10 · 2015: 12 · 2014: 18 · 2013: 18 · 2012: 20
- FWCI
- 6.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Cell Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Physical Performance
- Keywords
- myostatin, insulin-like growth factor I, Akt signaling, myotube hypertrophy, skeletal muscle growth, Akt phosphorylation, C2C12 myotubes, S6 phosphorylation, atrogin-1, muscle atrophy, myostatin propeptide, dominant-negative Akt
- MeSH terms
- Animals, Cell Line, Hypertrophy, Insulin-Like Growth Factor I, Blotting, Western, Mice, Knockout, Muscle Fibers, Skeletal, Reverse Transcriptase Polymerase Chain Reaction, Proto-Oncogene Proteins c-akt, Mice, Myostatin
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