Role of Parkin in the pathogenesis of COPD-related sarcopenia

Abstract

Introduction: Sarcopenia characterized by the loss of skeletal muscle mass and strength is prevalent in COPD. Sarcopenia has a huge impact on physical activity and is associated with increased mortality in COPD, but detailed molecular mechanism is still unclear. Increased reactive oxygen species (ROS) production and altered mitochondrial function has been reported in limb skeletal muscle of COPD. Previous study reported that muscle-specific depletion of autophagy was associated with increased ROS production in skeletal muscle. Although we have demonstrated the involvement of impaired Parkin-mediated mitochondria-selective autophagy, mitophagy in COPD pathogenesis, participation of mitophagy in sarcopenia progression associated with cigarette smoke (CS) exposure remains to be elucidated. Methods: Myoblasts were isolated from mouse limbs. CS extracts (CSE) was used to examine the effect of CS on myotube differentiation, reflecting myogenesis ability of myoblasts. Wild type (WT) myoblasts and Parkin knockout (KO) derived myoblasts were treated with 0.5 % CSE. Fusion index (the degree of differentiation from myoblast to myotube) and quantitative reverse transcription (RT)-PCR for myogenin (a marker for myotube differentiation) were performed. Results: Fusion index was significantly reduced by CSE exposure in WT myoblasts. Parkin KO myoblasts also showed reduced fusion index even in the absence of CSE. The expression levels of myogenin mRNA were decreased in CSE-exposed WT myoblasts and in Parkin KO myoblasts without CSE treatment. Conclusion: These results suggest that Parkin-mediated mitophagy may have a regulatory role in myogenesis during CS exposure as a part of sarcopenia pathogenesis in COPD.