Grant: Operating Grant

Muscle wasting is a significant problem in chronic obstructive pulmonary disease (COPD) which is associated with important clinical issues such as decreased functional status, reduced quality of life and increased mortality rate. Although accumulating knowledge reveals that contractile protein degradation is the primary mechanism involved in muscle wasting, factors initiating this process in COPD is still poorly understood. Low blood oxygen levels frequently presents in COPD increasing in severity as the disease progress. Lack of oxygen has been suggested to have the potential to trigger muscle loss in human subjects. In a model of cultured muscle cells, we found that low oxygen levels altered contractile protein homeostasis with a net loss in protein content as a consequence. In this research application, we propose to investigate the relationship between low oxygen levels and inflammation in the initiation of contractile protein degradation and the development of muscle atrophy. Greater understanding of the biochemical mechanisms that are involved in peripheral muscle wasting is important to design successful therapies aimed at reversing or stopping its progression and minimizing its adverse effects.