Indomethacin Preserves Muscle Mass and Reduces Levels of E3 Ligases and TNF Receptor Type 1 in the Gastrocnemius Muscle of Tumor-Bearing Mice
Format of Original
Research in Nursing and Health
Original Item ID
doi: 10.1002/nur.20057; Shelves: RT1 .R48x Raynor Memorial Periodicals
Tumor-induced skeletal muscle wasting involves tumor necrosis factor (TNF) and the ubiquitin-proteasome pathway of muscle protein degradation. In this study, growth of the colon-26 adenocarcinoma in mice was associated with diminished gastrocnemius muscle mass and increased muscle levels of actin, ubiquitin-conjugated proteins, free ubiquitin, E3 ubiquitin ligases, and the type 1 TNF receptor (TNFR1). Indomethacin at 1 or 5 mg/kg/day reduced tumor growth and muscle levels of TNFR1. However, only the 5 mg dose of indomethacin reduced muscle wasting and muscle levels of the E3 ligases and actin. These data suggest that the beneficial effects of indomethacin in the treatment of tumor-induced skeletal muscle wasting may involve inhibition of TNF- and ubiquitin-mediated pathways of muscle protein degradation. These data also demonstrate that E3 ligases, which are involved in disuse atrophy, also are associated with tumor-induced skeletal muscle wasting. © 2004 Wiley Periodicals, Inc. Res Nurs Health 28:56–66, 2005
Hitt, Andrew; Graves, Erin; and McCarthy, Donna O., "Indomethacin Preserves Muscle Mass and Reduces Levels of E3 Ligases and TNF Receptor Type 1 in the Gastrocnemius Muscle of Tumor-Bearing Mice" (2005). College of Nursing Faculty Research and Publications. 191.