caa a22 4500 445326573 CHVBK 20180317142722.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s10989-011-9264-x doi (NATIONALLICENCE)springer-10.1007/s10989-011-9264-x NMR Based Metabonomics Study of DAG Treatment in a C2C12 Mouse Skeletal Muscle Cell Line Myotube Model of Burn-Injury [Elektronische Daten] [Miki Watanabe, Sulaiman Sheriff, Theresa Ramelot, Nijiati Kadeer, Junho Cho, Kenneth Lewis, Ambikaipakan Balasubramaniam, Michael Kennedy] After severe burn injury, proinflammatory cytokine levels are elevated in serum and skeletal muscle, which in turn increases protein breakdown and decreases protein synthesis. In this study, C2C12 mouse skeletal muscle cell line myotubes were exposed to proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) as an in vitro cell-line model of catabolic response to burn injury and then treated with des-acyl ghrelin (DAG), a 28 amino acid polypeptide hormone thought to inhibit protein breakdown and increase protein synthesis, to assess its therapeutic potential. Nuclear magnetic resonance-based metabonomics was used to monitor metabolic activity of C2C12 myotubes under four treatment conditions: (1) control, (2) TNF-α/IFN-γ (TI), (3) DAG (DA), and (4) TNF-α/IFN-γ followed by DAG (TIDA) to assess the effect of DAG treatment on cellular metabolic response during basal or catabolic conditions. Twelve metabolites showed significant changes in concentrations following treatments in the hydrophilic cell extracts. Lactate (P<10−4) and citrulline (P<10−9) increased with TNF-α/IFN-γ treatment, indicating increased protein degradation, and returned to control levels in the TIDA group. Adenosine nucleotide levels had decreased trends in TI myotubes that returned to baseline levels after DAG treatment (P<10−4). Guanidinoacetate and pantothenate, metabolites involved in protein synthesis and cell proliferation, had increased concentration trends following DAG treatment in both the DA and TIDA groups. Our metabonomics analysis provides further evidence that DAG counteracts the catabolic response caused by elevated muscle TNF-α/IFN-γ cytokine levels following severe burns and can play a potential therapeutic role in treatment of burn injury. Springer Science+Business Media, LLC, 2011 NMR nationallicence Metabonomics nationallicence Metabolic profiling nationallicence C2C12 myotubes nationallicence Skeletal muscle cell nationallicence DAG nationallicence Burn injury nationallicence Protein breakdown nationallicence NMR : Nuclear magnetic resonance nationallicence PCA : Principal component analysis nationallicence DAG : Des-acyl ghrelin nationallicence TNF-α : Tumor necrosis factor-α nationallicence IFN-γ : Interferon-γ nationallicence TI : TNF-α/IFN-γ treated group nationallicence DA : DAG treated group nationallicence TIDA : TNF-α/IFN-γ followed by DAG treated group nationallicence TI/TIDA : Comparison between TI and TIDA group nationallicence EDL : Extensor digitorum longus nationallicence IGF-I : Insulin-like growth factor-I nationallicence Watanabe Miki Department of Chemistry and Biochemistry, Miami University, 106 Hughes Laboratories, 45056, Oxford, OH, USA aut Sheriff Sulaiman Department of Surgery, University of Cincinnati Medical Center, 45267, Cincinnati, OH, USA aut Ramelot Theresa Department of Chemistry and Biochemistry, Miami University, 106 Hughes Laboratories, 45056, Oxford, OH, USA aut Kadeer Nijiati Shriners Hospital for Children, 45229, Cincinnati, OH, USA aut Cho Junho Department of Chemistry and Biochemistry, Miami University, 106 Hughes Laboratories, 45056, Oxford, OH, USA aut Lewis Kenneth Department of Chemistry and Biochemistry, Miami University, 106 Hughes Laboratories, 45056, Oxford, OH, USA aut Balasubramaniam Ambikaipakan Department of Surgery, University of Cincinnati Medical Center, 45267, Cincinnati, OH, USA aut Kennedy Michael Department of Chemistry and Biochemistry, Miami University, 106 Hughes Laboratories, 45056, Oxford, OH, USA aut International Journal of Peptide Research and Therapeutics Springer Netherlands 17/4(2011-12-01), 281-299 1573-3149 17:4<281 2011 17 10989 https://doi.org/10.1007/s10989-011-9264-x text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10989-011-9264-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Watanabe Miki Department of Chemistry and Biochemistry, Miami University, 106 Hughes Laboratories, 45056, Oxford, OH, USA aut NATIONALLICENCE 700 1- Sheriff Sulaiman Department of Surgery, University of Cincinnati Medical Center, 45267, Cincinnati, OH, USA aut NATIONALLICENCE 700 1- Ramelot Theresa Department of Chemistry and Biochemistry, Miami University, 106 Hughes Laboratories, 45056, Oxford, OH, USA aut NATIONALLICENCE 700 1- Kadeer Nijiati Shriners Hospital for Children, 45229, Cincinnati, OH, USA aut NATIONALLICENCE 700 1- Cho Junho Department of Chemistry and Biochemistry, Miami University, 106 Hughes Laboratories, 45056, Oxford, OH, USA aut NATIONALLICENCE 700 1- Lewis Kenneth Department of Chemistry and Biochemistry, Miami University, 106 Hughes Laboratories, 45056, Oxford, OH, USA aut NATIONALLICENCE 700 1- Balasubramaniam Ambikaipakan Department of Surgery, University of Cincinnati Medical Center, 45267, Cincinnati, OH, USA aut NATIONALLICENCE 700 1- Kennedy Michael Department of Chemistry and Biochemistry, Miami University, 106 Hughes Laboratories, 45056, Oxford, OH, USA aut NATIONALLICENCE 773 0- International Journal of Peptide Research and Therapeutics Springer Netherlands 17/4(2011-12-01), 281-299 1573-3149 17:4<281 2011 17 10989 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer