Ubiquitin ligase gene expression in healthy volunteers with 20-day bedrest.
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.
Ogawa
Takayuki
T
Department of Orthopaedics, University of Tokushima School of Medicine, Tokushima, Japan.
Furochi
Harumi
H
Mameoka
Mai
M
Hirasaka
Katsuya
K
Onishi
Yuko
Y
Suzue
Naoto
N
Oarada
Motoko
M
Akamatsu
Motoki
M
Akima
Hiroshi
H
Fukunaga
Tetsuo
T
Kishi
Kyoichi
K
Yasui
Natsuo
N
Ishidoh
Kazumi
K
Fukuoka
Hideoki
H
Nikawa
Takeshi
T
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D001510:Bed Rest / Q000009:adverse effects*; D001835:Body Weight / Q000235:genetics / Q000502:physiology; D004247:DNA / Q000235:genetics; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D008297:Male; D009124:Muscle Proteins / Q000235:genetics* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology; D009133:Muscular Atrophy / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D009929:Organ Size / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000378:metabolism; D050721:Proto-Oncogene Proteins c-cbl / Q000235:genetics* / Q000378:metabolism; D044843:SKP Cullin F-Box Protein Ligases / Q000235:genetics* / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics* / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D009124:Muscle Proteins; D011506:Proteins; D004247:DNA; C492211:CBLB protein, human; C440907:FBXO32 protein, human; D050721:Proto-Oncogene Proteins c-cbl; D044843:SKP Cullin F-Box Protein Ligases; D044767:Ubiquitin-Protein Ligases