RGD Reference Report - Transcription factors in muscle atrophy caused by blocked neuromuscular transmission and muscle unloading in rats. - Rat Genome Database

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Transcription factors in muscle atrophy caused by blocked neuromuscular transmission and muscle unloading in rats.

Authors: Nordquist, J  Hoglund, AS  Norman, H  Tang, X  Dworkin, B  Larsson, L 
Citation: Nordquist J, etal., Mol Med. 2007 Sep-Oct;13(9-10):461-70.
RGD ID: 4892297
Pubmed: PMID:17622304   (View Abstract at PubMed)
PMCID: PMC2014727   (View Article at PubMed Central)
DOI: DOI:10.2119/2006-00066.Nordquist   (Journal Full-text)

The muscle wasting associated with long-term intensive care unit (ICU) treatment has a negative effect on muscle function resulting in prolonged periods of rehabilitation and a decreased quality of life. To identify mechanisms behind this form of muscle wasting, we have used a rat model designed to mimic the conditions in an ICU. Rats were pharmacologically paralyzed with a postsynaptic blocker of neuromuscular transmission, and mechanically ventilated for one to two weeks, thereby unloading the limb muscles. Transcription factors were analyzed for cellular localization and nuclear concentration in the fast-twitch muscle extensor digitorum longus (EDL) and in the slow-twitch soleus. Significant muscle wasting and upregulation of mRNA for the ubiquitin ligases MAFbx and MuRF1 followed the treatment. The IkappaB family-member Bcl-3 displayed a concomitant decrease in concentration, suggesting altered kappaB controlled gene expression, although NFkappaB p65 was not significantly affected. The nuclear levels of the glucocorticoid receptor (GR) and the thyroid receptor alpha1 (TRalpha1) were altered and also suggested as potential mediators of the MAFbx- and MuRF1-induction in the absence of induced Foxo1. We believe that this model, and the strategy of quantifying nuclear proteins, will provide a valuable tool for further, more detailed, analyses of the muscle wasting occurring in patients kept on a mechanical ventilator.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nr3c1Ratmuscular atrophy  IEP protein:altered expression:nucleusRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Nr3c1Ratmuscle atrophy  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nr3c1  (nuclear receptor subfamily 3, group C, member 1)


Additional Information