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Indomethacin preserves muscle mass and reduces levels of E3 ligases and TNF receptor type 1 in the gastrocnemius muscle of tumor‐bearing mice
Author(s) -
Hitt Andrew,
Graves Erin,
McCarthy Donna O.
Publication year - 2005
Publication title -
research in nursing and health
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.836
H-Index - 85
eISSN - 1098-240X
pISSN - 0160-6891
DOI - 10.1002/nur.20057
Subject(s) - gastrocnemius muscle , receptor , tumor necrosis factor alpha , bearing (navigation) , medicine , endocrinology , skeletal muscle , cartography , geography
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