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J Muscle Res Cell Motil. 2017 Apr;38(2):201-214. doi: 10.1007/s10974-017-9473-9. Epub 2017 Jun 20.

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

Author information

1
Division of Natural Sciences and Engineering, University of South Carolina Upstate, Spartanburg, SC, 29303, USA.
2
Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, NC, 28403-5915, USA.
3
Division of Natural Sciences and Engineering, University of South Carolina Upstate, Spartanburg, SC, 29303, USA. bbaumgar@uscupstate.edu.

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:

Autophagy; Caffeine; Myostatin; Protein synthesis; Skeletal muscle

PMID:
28634643
PMCID:
PMC5660649
DOI:
10.1007/s10974-017-9473-9
[Indexed for MEDLINE]
Free PMC Article

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