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Show allStudy of the Relation between Hypoxia and Muscle Atrophy
Abstract
Background : Skeletal muscle atrophy is an important feature of chronic obstructive pulmonary disease (COPD) and it is recognized to have considerable clinical impacts. Unfortunately, factors contributing to muscle wasting in COPD are poorly understood. Hypoxemia is typical in COPD and several evidences link hypoxic conditions and protein breakdown. We propose that hypoxia participate to muscle atrophy by increasing Ubiquitin-Proteasome (UP) system activity and by decreasing the activity of IGF/PI3K/Akt synthesis pathway.
Methods: To test this hypothesis, L6 muscle myotubes were either exposed to hypoxia (1% O2) or normoxia (21% O2).
Results: After 24 hours of hypoxic exposure, we found a significant rise in the chymotrypsin and caspase-like 20S proteasome activities. Proteolysis was confirmed by an accumulation of a 14 kDa actin fragment during hypoxia. An elevation of Atrogin-1 mRNA expression was also observed in similar conditions. A decline in Akt phosphorylation was noticed in hypoxia. These changes were attenuated by insulin treatment.
Conclusion: Proteolysis is accentuated in myotubes exposed to hypoxia and the UP system appears to be involved. In addition, protein synthesis seems to be affected as a lower Akt activity was observed. However, the IGF/PI3K/Akt pathway can still be stimulated by a suitable signal suggesting that therapies targeting this pathway are conceivable.
Methods: To test this hypothesis, L6 muscle myotubes were either exposed to hypoxia (1% O2) or normoxia (21% O2).
Results: After 24 hours of hypoxic exposure, we found a significant rise in the chymotrypsin and caspase-like 20S proteasome activities. Proteolysis was confirmed by an accumulation of a 14 kDa actin fragment during hypoxia. An elevation of Atrogin-1 mRNA expression was also observed in similar conditions. A decline in Akt phosphorylation was noticed in hypoxia. These changes were attenuated by insulin treatment.
Conclusion: Proteolysis is accentuated in myotubes exposed to hypoxia and the UP system appears to be involved. In addition, protein synthesis seems to be affected as a lower Akt activity was observed. However, the IGF/PI3K/Akt pathway can still be stimulated by a suitable signal suggesting that therapies targeting this pathway are conceivable.
© 2007-2012 Canadian Society for Clinical Investigation.
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