Effects of limb immobilization on cytochrome c oxidase activity and GLUT4 and GLUT5 protein expression in human skeletal muscle.

Abstract

1. We investigated the effects of limb immobilization (for 1 or 6 weeks) in a long leg cast after a closed tibial fracture (n = 11). Biopsies of vastus lateralis were taken on admission and after either 1 week (n = 5) or 6 weeks (n = 6) and analysed for muscle fibre type characteristics, cytochrome c oxidase activity and the abundance of GLUT4 and GLUT5 hexose transporters. 2. After 1 week of immobilization there was a significant decrease (8%) in the cross-sectional area of type I, but not type II, muscle fibers and in the protein-DNA ratio (16%) compared with the initial biopsy. Six weeks of immobilization led to further muscle atrophy compared with the initial biopsy and a further reduction in the cross-sectional area of both type I and II fibres (29% and 36% decrease respectively) and in the protein-DNA ratio (25%). No changes were observed in the free leg after 1 week. However, at th end of the 6 week study period, the cross-sectional area of boty type I and II fibres of the free leg were increased (7% and 5%) and there was significant increase in the protein-DNA ratio (14%), indicating a net increase in muscle protein content. 3. Assay for cytochrome c oxidase activity showed significant reduction after 1 (30%) or 6 weeks (36%) of immobilization, reflecting a reduced capacity for oxidative metabolism. No significant changes in activity were observed in muscle from the free leg after 1 or 6 weeks of study. 4. The concentrations of GLUT4 and GLUT5 protein were determined by Western blot analysis. Limb immobilization induced a marked (50%) reduction in muscle GLUT4 protein concentration after 1 week that persisted for 6 weeks. A transient but significant increase (approximately twofold) in GLUT4 concentration was detected in muscle from the free leg after 1 week, but this returned to pre-imobilization values at 6 week. Unlike GLUT4, no significant changes in the abundance of the GLUT5 protein were detected in either the immobilized or free leg at the end of the 1 or 6 week periods. 5. The present findings indicate that disuse rapidly induces a selective loss of activity and abundance of some non-myofibrillar proteins in humans. The decrease in GLUT4 protein abundance and cytochrome c oxidase activity during muscle disuse is consistent with a decreased capacity for glucose uptake and with a lower oxidative potential of inactive muscle. The lack of any major changes in GLUT5 protein abundance during limb immobilization indicates that the expression of some non-myofibrillar proteins is differentially regulated in response to muscle disuse.

• Authors: S J Blakemore, P K Rickhuss, P W Watt, M J Rennie, H S Hundal
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 91 Issue 5 Pg. 591-9 (Nov 1996) ISSN: 0143-5221 [Print] England
• PMID: 8942398 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Glucose Transporter Type 4
• Glucose Transporter Type 5
• Monosaccharide Transport Proteins
• Muscle Proteins
• SLC2A4 protein, human
• DNA
• Electron Transport Complex IV

Topics

• Adult
• Blotting, Western
• DNA (metabolism)
• Electron Transport Complex IV (metabolism)
• Female
• Glucose Transporter Type 4
• Glucose Transporter Type 5
• Humans
• Immobilization (physiology)
• Leg
• Male
• Middle Aged
• Monosaccharide Transport Proteins (metabolism)
• Muscle Proteins (metabolism)
• Muscle, Skeletal (metabolism, pathology)
• Random Allocation
• Time Factors