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KMID : 0613820180280040435
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Journal of Life Science
2018 Volume.28 No. 4 p.435 ~ p.443
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Ethanol Extract of Mori Folium Inhibits AICAR-induced Muscle Atrophy Through Inactivation of AMPK in C2C12 Myotubes
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Lee Yu-Sung
Kim Hong-Jae
Jeong Jin-Woo
Han Min-Ho
Hong Su-Hyun
Choi Yung-Hyun
Park Cheol
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Abstract
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AMP-activated protein kinase (AMPK) functions as a metabolic master through regulating and restoring cellular energy balance. In skeletal muscle, AMPK increases myofibril protein degradation through the expression of muscle-specific ubiquitin ligases. Mori Folium, the leaf of Morus alba, is a traditional medicinal herb with various pharmacological functions; however, the effects associated with muscle atrophy have not been fully identified. In this study, we confirmed the effects of AMPK activation by examining the effects of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), an activator of AMPK, on the induction of atrophy and expression of atrophy-related genes in C2C12 myotubes. We also investigated the effects of the ethanol extract of Mori Folium (EEMF) on the recovery of AICAR-induced muscle atrophy in C2C12 myotubes. It was found that exposure to AICAR resulted in the stimulation of Forkhead box O3a (FOXO3a); an up-regulation of muscle-specific ubiquitin ligases such as Muscle Atrophy F-box (MAFbx)/atrogin-1 and muscle RING finger-1 (MuRF1), and a down-regulation of muscle-specific transcription factors, such as MyoD and myogenin; with the activation of AMPK. In addition, AICAR without cytotoxicity indicated a decrease in diameter of C2C12 myotubes. However, treatment with EEMF significantly suppressed AICAR-induced muscle atrophy of C2C12 myotubes in a dose-dependent manner as confirmed by a decrease in myotube diameter, which is associated with a reversed stimulation of FOXO3a by the inhibition of AMPK activation. These results indicate that the activation of AMPK by AICAR induces muscle atrophy, and EEMF has preeminent effects on the inhibition of AICAR-induced muscle atrophy through the AMPK signaling pathway.
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KEYWORD
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AICAR, AMPK, atrophy, C2C12 myotubes, EEMF
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