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Journal of Muscle Research and Cell Motility

, Volume 38, Issue 2, pp 201–214 | Cite as

Acute high-caffeine exposure increases autophagic flux and reduces protein synthesis in C2C12 skeletal myotubes

  • M. A. Hughes
  • R. M. Downs
  • G. W. Webb
  • C. L. Crocker
  • S. T. Kinsey
  • Bradley L. BaumgarnerEmail author
Article

Abstract

Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1–10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux. In contrast, caffeine treatment did not significantly increase the expression of the skeletal muscle specific ubiquitin ligases MAFbx and MuRF1 or 20S proteasome activity. Caffeine treatment significantly reduced mTORC1 signaling, total protein synthesis and myotube diameter in a CaMKKβ/AMPK-dependent manner. Further, caffeine promoted a CaMKII-dependent increase in myostatin mRNA expression that did not significantly contribute to the caffeine-dependent reduction in protein synthesis. Our results indicate that short-term caffeine exposure significantly reduced skeletal myotube diameter by increasing autophagic flux and promoting a CaMKKβ/AMPK-dependent reduction in protein synthesis.

Keywords

Caffeine Skeletal muscle Protein synthesis Autophagy Myostatin 

Notes

Acknowledgements

Financial support was provided by Magellan Scholars Fellowships that were awarded by the Office of Undergraduate Research at the University of South Carolina to M. A. Hughes. Additional support was provided by a Magellan Mentors Award that was awarded by the University of South Carolina Upstate Office of Sponsored Awards and Research Support to B. L. Baumgarner. Research reported in this publication was also supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under Award Number R15DK106688 to S. T. Kinsey.

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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  • M. A. Hughes
    • 1
  • R. M. Downs
    • 1
  • G. W. Webb
    • 1
  • C. L. Crocker
    • 2
  • S. T. Kinsey
    • 2
  • Bradley L. Baumgarner
    • 1
    Email author
  1. 1.Division of Natural Sciences and EngineeringUniversity of South Carolina UpstateSpartanburgUSA
  2. 2.Department of Biology and Marine BiologyUniversity of North Carolina WilmingtonWilmingtonUSA

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