Little change in markers of protein breakdown and oxidative stress in humans in immobilization-induced skeletal muscle atrophy.
A number of studies in rodents suggest that disuse atrophy results from a large increase in proteolysis affected by, or accompanying, increased oxidative stress. Little information is available, however, about the effects of immobilization on markers of muscle protein breakdown and oxidative stress in humans. Therefore, the purpose of this investigation was to measure markers of breakdown or oxidative stress in subjects who underwent 14 days of knee-brace-mediated immobilization. Vastus lateralis samples taken from 21 young subjects before, and 2 days and 14 days after, single leg immobilization were measured for ubiquitin-protein conjugates, caspase 3/7 activity, the 14-kDa caspase-3 cleaved actin fragment, 4-hydroxy-2-nonenal (4-HNE) adducts, and protein carbonyls. Quadriceps cross-sectional area decreased by 5.7% +/- 1.1% (p < 0.0001) following immobilization. Ubiquitin-protein conjugates were elevated at 2 days of immobilization (12%, p < 0.05) but were not different from baseline at 14 days. Levels of the 14-kDa actin fragment and caspase 3/7 activity did not change over the immobilization period. The oxidative stress markers, 4-HNE adducts and protein carbonyls, did not change at any time point. These static measures of breakdown and oxidative modification suggest that a small increase in protein ubiquitination occurs early (2 days), but elevations in ubiquitinated or oxidatively modified proteins are not sustained during the later phase (14 days) of uncomplicated disuse atrophy in humans, suggesting that these pathways are not playing a major role in simple disuse-induced atrophic loss of protein mass.
Glover
Elisa I
EI
Department of Kinesiology-Exercise Metabolic Research Group, McMaster University, Hamilton, Ontario, Canada.
Yasuda
Nobuo
N
Tarnopolsky
Mark A
MA
Abadi
Arkan
A
Phillips
Stuart M
SM
D000199:Actins / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D001915:Braces; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism*; D009133:Muscular Atrophy / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000378:metabolism; D050050:Protein Carbonylation; D011499:Protein Processing, Post-Translational; D052097:Quadriceps Muscle / Q000378:metabolism* / Q000473:pathology; D012149:Restraint, Physical; D013997:Time Factors; D054875:Ubiquitination
D000199:Actins; D000447:Aldehydes; D015415:Biomarkers; D009124:Muscle Proteins; D010446:Peptide Fragments; C033025:actin subfragments; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7; C027576:4-hydroxy-2-nonenal