Caffeine promotes autophagy in skeletal muscle cells by increasing the calcium-dependent activation of AMP-activated protein kinase

Biochem Biophys Res Commun. 2014 Oct 24;453(3):411-8. doi: 10.1016/j.bbrc.2014.09.094. Epub 2014 Sep 28.

Abstract

Caffeine has been shown to promote calcium-dependent activation of AMP-activated protein kinase (AMPK) and AMPK-dependent glucose and fatty acid uptake in mammalian skeletal muscle. Though caffeine has been shown to promote autophagy in various mammalian cell lines it is unclear if caffeine-induced autophagy is related to the calcium-dependent activation of AMPK. The purpose of this study was to examine the role of calcium-dependent AMPK activation in regulating caffeine-induced autophagy in mammalian skeletal muscle cells. We discovered that the addition of the AMPK inhibitor Compound C could significantly reduce the expression of the autophagy marker microtubule-associated protein 1 light chain 3b-II (LC3b-II) and autophagic vesicle accumulation in caffeine treated skeletal muscle cells. Additional experiments using pharmacological inhibitors and RNA interference (RNAi) demonstrated that the calcium/calmodulin-activated protein kinases CaMKKβ and CaMKII contributed to the AMPK-dependent expression of LC3b-II and autophagic vesicle accumulation in a caffeine dose-dependent manner. Our results indicate that in skeletal muscle cells caffeine increases autophagy by promoting the calcium-dependent activation of AMPK.

Keywords: AMP-activated protein kinase; Autophagy; Caffeine; Calcium; Calcium/calmodulin-activated protein kinase II.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Autophagy / drug effects*
  • Caffeine / pharmacology*
  • Calcium / metabolism*
  • Cell Line
  • Enzyme Activation
  • Mice
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / enzymology

Substances

  • Caffeine
  • AMP-Activated Protein Kinases
  • Calcium