Ubiquitin Ligase Gene Expression in Healthy Volunteers With 20-day Bedrest

Muscle Nerve. 2006 Oct;34(4):463-9. doi: 10.1002/mus.20611.

Abstract

In animal models, several ubiquitin ligases play an important role in skeletal muscle atrophy caused by unloading. In this study we examined protein ubiquitination and ubiquitin ligase gene expression in quadriceps femoris muscle from healthy volunteers after 20-day bedrest to clarify ubiquitin-dependent proteolysis in human muscles after unloading. During bedrest, thickness and cross-sectional area of the quadriceps femoris muscle decreased significantly by 4.6% and 3.7%, respectively. Ubiquitinated proteins accumulated in these atrophied human muscles. A real-time reverse transcription-polymerase chain reaction system showed that bedrest significantly upregulated expression of two ubiquitin ligase genes, Cbl-b and atrogin-1. We also performed DNA microarray analysis to examine comprehensive gene expression in the atrophied muscle. Bedrest mainly suppressed the expression of muscle genes associated with control of gene expression in skeletal muscle. Our results suggest that, in humans, Cbl-b- or atrogin-1-mediated ubiquitination plays an important role in unloading-induced muscle atrophy, and that unloading stress may preferentially inhibit transcriptional responses in skeletal muscle.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Bed Rest / adverse effects*
  • Body Weight / genetics
  • Body Weight / physiology
  • DNA / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Male
  • Muscle Proteins / genetics*
  • Muscle Proteins / metabolism
  • Muscle, Skeletal / enzymology*
  • Muscle, Skeletal / pathology
  • Muscular Atrophy / enzymology*
  • Muscular Atrophy / etiology
  • Muscular Atrophy / genetics
  • Oligonucleotide Array Sequence Analysis
  • Organ Size / genetics
  • Organ Size / physiology
  • Proteins / metabolism
  • Proto-Oncogene Proteins c-cbl / genetics*
  • Proto-Oncogene Proteins c-cbl / metabolism
  • SKP Cullin F-Box Protein Ligases / genetics*
  • SKP Cullin F-Box Protein Ligases / metabolism
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • Muscle Proteins
  • Proteins
  • DNA
  • CBLB protein, human
  • FBXO32 protein, human
  • Proto-Oncogene Proteins c-cbl
  • SKP Cullin F-Box Protein Ligases
  • Ubiquitin-Protein Ligases