title: Caffeine promotes autophagy in skeletal muscle cells by increasing the calcium-dependent activation of AMP-activated protein kinase.
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.
authors.affiliation: Division of Natural Sciences and Engineering, University of South Carolina Upstate, Spartanburg, SC, USA.
authors.forename: T S
authors.initials: TS
authors.lastname: Mathew
authors.affiliation: Division of Natural Sciences and Engineering, University of South Carolina Upstate, Spartanburg, SC, USA.
authors.forename: R K
authors.initials: RK
authors.lastname: Ferris
authors.affiliation: Division of Natural Sciences and Engineering, University of South Carolina Upstate, Spartanburg, SC, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Downs
authors.affiliation: Department of Biology and Marine Biology, University of North Carolina Wilmington, Wilmington, NC, USA.
authors.forename: S T
authors.initials: ST
authors.lastname: Kinsey
authors.affiliation: Division of Natural Sciences and Engineering, University of South Carolina Upstate, Spartanburg, SC, USA. Electronic address: bbaumgar@uscupstate.edu.
authors.forename: B L
authors.initials: BL
authors.lastname: Baumgarner
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004789:Enzyme Activation; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology
chemical_list: D002110:Caffeine; D055372:AMP-Activated Protein Kinases; D002118:Calcium
keywords: AMP-activated protein kinase; Autophagy; Caffeine; Calcium; Calcium/calmodulin-activated protein kinase II