کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1928422 | 1050355 | 2014 | 8 صفحه PDF | دانلود رایگان |

• Caffeine promotes autophagy by increasing calcium-dependent activation of AMPK.
• CaMKII contributes to AMPK phosphorylation in caffeine treated muscle cells.
• CaMKII contributes to LC3b-II expression, but not autophagosome accumulation.
• The primary mechanism of caffeine-induced autophagy is CaMKKβ activation of AMPK.
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.
Journal: Biochemical and Biophysical Research Communications - Volume 453, Issue 3, 24 October 2014, Pages 411–418