Different fiber-specific expression of protein synthesis and oxidative metabolism in skeletal muscle of COPD and healthy aged individuals

Patients with chronic obstructive pulmonary disease (COPD) show low muscle oxidative capacity, a shift toward a fast-type II muscle fiber type, and a reduced cross-sectional area of skeletal muscle fibers. Here we compared the level of protein synthesis and oxidative metabolism protein pathways in type I and IIa muscle fibers from COPD and healthy aged individuals. Ten COPD and eight healthy individuals underwent a muscle biopsy from the vastus lateralis. Total ubiquitination, Akt-1, p70s6K, S6 ribosomal protein, OXPHOS, COX-IV, MCU, Mitofusin2, DRP1, and AMPK proteins from whole muscle and fiber-type pooled samples were quantified by Western blot. Indirect immunofluorescence was used to assess fiber morphology. Total levels of Akt-1, S6RP, AMPK, and MCU protein were similar between muscle fiber types, and in whole muscle homogenates between COPD and healthy individuals. COPD patients showed greater levels of p70S6k in whole muscle, and IIa muscle fiber. Both groups showed greater levels of MCU in type I fibers. COPD patients showed lesser levels of COX IV and subunits I-IV of OXPHOS compared to healthy. Total protein ubiquitination was greater in COPD than in healthy, which was greater in type IIa fibers, opposite to healthy, which showed greater levels of ubiquitination of type I fibers. Mitofusin2 and DRP1 proteins were greater in COPD compared to healthy. These results suggest that COPD patients have compensatory machinery for protein synthesis and oxidative metabolism in response to greater ubiquitination and autophagy, particularly in type IIa fibers.