Induction of MuRF1 Is Essential for TNF-α-Induced Loss of Muscle Function in Mice

Humoral circulating inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) can impair skeletal muscle contractility. Furthermore, TNF-α expression correlates with elevated levels of atrogin-like muscle-specific ubiquitin E3 ligases, which are presumed to mediate muscle protein breakdown...

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Bibliographic Details
Published in:Journal of molecular biology 2008-12, Vol.384 (1), p.48-59
Main Authors: Adams, Volker, Mangner, Norman, Gasch, Alexander, Krohne, Christian, Gielen, Stephan, Hirner, Stephanie, Thierse, Hermann-Josef, Witt, Christian C., Linke, Axel, Schuler, Gerhard, Labeit, Siegfried
Format: Article
Language:English
Subjects:
Animals
Cell Line
cytokines
Down-Regulation - drug effects
Eukaryotic Initiation Factor-4E - metabolism
Immunoprecipitation
In Vitro Techniques
Mice
Models, Biological
MuRF1
Muscle Contraction - drug effects
Muscle Fibers, Skeletal - cytology
Muscle Fibers, Skeletal - drug effects
Muscle Fibers, Skeletal - metabolism
Muscle Proteins - genetics
Muscle Proteins - metabolism
Muscle, Skeletal - cytology
Muscle, Skeletal - drug effects
Muscle, Skeletal - physiology
myopathy
Peptide Elongation Factor 1 - metabolism
skeletal muscle function
Tripartite Motif Proteins
Troponin T - metabolism
Tumor Necrosis Factor-alpha - pharmacology
Ubiquitin - metabolism
ubiquitin E3 ligases
Ubiquitin-Protein Ligases - genetics
Ubiquitin-Protein Ligases - metabolism
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Summary:Humoral circulating inflammatory cytokines such as tumor necrosis factor alpha (TNF-α) can impair skeletal muscle contractility. Furthermore, TNF-α expression correlates with elevated levels of atrogin-like muscle-specific ubiquitin E3 ligases, which are presumed to mediate muscle protein breakdown and atrophy. However, the casual relationships between MuRF1 and TNF-α and their relative contributions to muscle function impairment are not known. TNF-α or saline was injected into either C57Bl6 or MuRF1−/− mice. After 16–24 h, the expression of MuRF1 in skeletal muscle was quantified by quantitative reverse transcription–PCR and Western blot analysis. Muscle function was measured in an organ bath. To obtain a broader overview on potential alterations, two-dimensional gel electrophoresis was performed. Wild-type animals injected with TNF-α had higher MuRF1 mRNA expression (saline versus TNF-α: 56.6±12.1 versus 133.6±30.3 arbitrary units; p
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2008.08.087