Des-acyl ghrelin exhibits pro-anabolic and anti-catabolic effects on C2C12 myotubes exposed to cytokines and reduces burn-induced muscle proteolysis in rats

作者：Sheriff Sulaiman; Kadeer Nijiati; Joshi Rashika; Friend Lou Ann; James J Howard; Balasubramaniam Arnbikaipakan^*

来源：Molecular and Cellular Endocrinology, 2012, 351(2): 286-295.

DOI：10.1016/j.mce.2011.12.021

• Atrophy
• Burn injury
• Hypertrophy
• Muscle cachexia
• Signaling pathways

Although ghrelin and GHRP-2 have been shown to inhibit skeletal muscle proteolysis in rats with burn injury, the effects of des-acyl ghrelin (DAG) have not been reported. In this paper, we demonstrate that continuous 24 h administration of DAG attenuated burn-induced EDL muscle proteolysis, and normalized elevated TNF alpha mRNA. Combined treatment of cultured C2C12 myotubes with TNF alpha and IFN-gamma (TNF + IFN) inhibited protein synthesis and increased protein breakdown; DAG abolished both effects. PI3 kinase inhibition by LY294002 and mTOR inhibition by rapamycin blocked the reversal of the anti-anabolic effects of TNF + IFN-treated myotubes by DAG. DAG also reversed or attenuated the TNF + IFN-induced reduction in phosphorylation of Akt, FOXO1, 4E-BP-1, and GSK-3 beta in myotubes. Furthermore, DAG attenuated the atrophy signal, phospho-NF-kappa B, and the mRNA expression of MAFbx and MuRF1, upregulated by TNF + IFN in C2C12 myotubes. We conclude that DAG reduces muscle cachexia produced by injury and proinflammatory cytokines, and that DAG or DAG-based compounds may be useful in treating wasting disorders. Published by Elsevier Ireland Ltd.

• 出版日期2012-4-4