Gene interactions and pathways from curated databases and text-mining
Mol Cell Endocrinol 2012, PMID: 22266196

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

Sheriff, Sulaiman; Kadeer, Nijiati; Joshi, Rashika; Friend, Lou Ann; James, J Howard; Balasubramaniam, Ambikaipakan

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 24h administration of DAG attenuated burn-induced EDL muscle proteolysis, and normalized elevated TNFα mRNA. Combined treatment of cultured C2C12 myotubes with TNFα and IFN-γ (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-3β in myotubes. Furthermore, DAG attenuated the atrophy signal, phospho-NF-κB, 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.

Diseases/Pathways annotated by Medline MESH: Burns, Cachexia
Document information provided by NCBI PubMed

Text Mining Data

mTOR ⊣ PI3: " 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 "

FOXO1 ⊣ TNF+IFN: " DAG also reversed or attenuated the TNF+IFN induced reduction in phosphorylation of Akt, FOXO1 , 4E-BP-1, and GSK-3ß in myotubes "

4E-BP-1 ⊣ TNF+IFN: " DAG also reversed or attenuated the TNF+IFN induced reduction in phosphorylation of Akt, FOXO1, 4E-BP-1 , and GSK-3ß in myotubes "

FOXO1 ⊣ TNF+IFN: " DAG also reversed or attenuated the TNF+IFN induced reduction in phosphorylation of Akt, FOXO1 , 4E-BP-1, and GSK-3ß in myotubes "

Akt ⊣ TNF+IFN: " DAG also reversed or attenuated the TNF+IFN induced reduction in phosphorylation of Akt , FOXO1, 4E-BP-1, and GSK-3ß in myotubes "

4E-BP-1 ⊣ TNF+IFN: " DAG also reversed or attenuated the TNF+IFN induced reduction in phosphorylation of Akt, FOXO1, 4E-BP-1 , and GSK-3ß in myotubes "

Manually curated Databases

No curated data.