Skip to main content
Journal cover image

Cessation of biomechanical stretch model of C2C12 cells models myocyte atrophy and anaplerotic changes in metabolism using non-targeted metabolomics analysis.

Publication ,  Journal Article
Ilaiwy, A; Quintana, MT; Bain, JR; Muehlbauer, MJ; Brown, DI; Stansfield, WE; Willis, MS
Published in: Int J Biochem Cell Biol
October 2016

Studies of skeletal muscle disuse, either in patients on bed rest or experimentally in animals (immobilization), have demonstrated that decreased protein synthesis is common, with transient parallel increases in protein degradation. Muscle disuse atrophy involves a process of transition from slow to fast myosin fiber types. A shift toward glycolysis, decreased capacity for fat oxidation, and substrate accumulation in atrophied muscles have been reported, as has accommodation of the liver with an increased gluconeogenic capacity. Recent studies have modeled skeletal muscle disuse by using cyclic stretch of differentiated myotubes (C2C12), which mimics the loading pattern of mature skeletal muscle, followed by cessation of stretch. We utilized this model to determine the metabolic changes using non-targeted metabolomics analysis of the media. We identified increases in amino acids resulting from muscle atrophy-induced protein degradation (largely sarcomere) that occurs with muscle atrophy that are involved in feeding the Kreb's cycle through anaplerosis. Specifically, we identified increased alanine/proline metabolism (significantly elevated proline, alanine, glutamine, and asparagine) and increased α-ketoglutaric acid, the proposed Kreb's cycle intermediate being fed by the alanine/proline metabolic anaplerotic mechanism. Additionally, several unique pathways not clearly delineated in previous studies of muscle unloading were seen, including: (1) elevated keto-acids derived from branched chain amino acids (i.e. 2-ketoleucine and 2-keovaline), which feed into a metabolic pathway supplying acetyl-CoA and 2-hydroxybutyrate (also significantly increased); and (2) elevated guanine, an intermediate of purine metabolism, was seen at 12h unloading. Given the interest in targeting different aspects of the ubiquitin proteasome system to inhibit protein degradation, this C2C12 system may allow the identification of direct and indirect alterations in metabolism due to anaplerosis or through other yet to be identified mechanisms using a non-targeted metabolomics approach.

Duke Scholars

Published In

Int J Biochem Cell Biol

DOI

EISSN

1878-5875

Publication Date

October 2016

Volume

79

Start / End Page

80 / 92

Location

Netherlands

Related Subject Headings

  • Muscular Atrophy
  • Mice
  • Metabolomics
  • Mechanical Phenomena
  • Cell Line
  • Biomechanical Phenomena
  • Biochemistry & Molecular Biology
  • Animals
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Ilaiwy, A., Quintana, M. T., Bain, J. R., Muehlbauer, M. J., Brown, D. I., Stansfield, W. E., & Willis, M. S. (2016). Cessation of biomechanical stretch model of C2C12 cells models myocyte atrophy and anaplerotic changes in metabolism using non-targeted metabolomics analysis. Int J Biochem Cell Biol, 79, 80–92. https://doi.org/10.1016/j.biocel.2016.08.012
Ilaiwy, Amro, Megan T. Quintana, James R. Bain, Michael J. Muehlbauer, David I. Brown, William E. Stansfield, and Monte S. Willis. “Cessation of biomechanical stretch model of C2C12 cells models myocyte atrophy and anaplerotic changes in metabolism using non-targeted metabolomics analysis.Int J Biochem Cell Biol 79 (October 2016): 80–92. https://doi.org/10.1016/j.biocel.2016.08.012.
Ilaiwy A, Quintana MT, Bain JR, Muehlbauer MJ, Brown DI, Stansfield WE, et al. Cessation of biomechanical stretch model of C2C12 cells models myocyte atrophy and anaplerotic changes in metabolism using non-targeted metabolomics analysis. Int J Biochem Cell Biol. 2016 Oct;79:80–92.
Ilaiwy, Amro, et al. “Cessation of biomechanical stretch model of C2C12 cells models myocyte atrophy and anaplerotic changes in metabolism using non-targeted metabolomics analysis.Int J Biochem Cell Biol, vol. 79, Oct. 2016, pp. 80–92. Pubmed, doi:10.1016/j.biocel.2016.08.012.
Ilaiwy A, Quintana MT, Bain JR, Muehlbauer MJ, Brown DI, Stansfield WE, Willis MS. Cessation of biomechanical stretch model of C2C12 cells models myocyte atrophy and anaplerotic changes in metabolism using non-targeted metabolomics analysis. Int J Biochem Cell Biol. 2016 Oct;79:80–92.
Journal cover image

Published In

Int J Biochem Cell Biol

DOI

EISSN

1878-5875

Publication Date

October 2016

Volume

79

Start / End Page

80 / 92

Location

Netherlands

Related Subject Headings

  • Muscular Atrophy
  • Mice
  • Metabolomics
  • Mechanical Phenomena
  • Cell Line
  • Biomechanical Phenomena
  • Biochemistry & Molecular Biology
  • Animals
  • 3205 Medical biochemistry and metabolomics
  • 3101 Biochemistry and cell biology