Abstract
Skeletal muscle atrophy occurs under various conditions, such as disuse, denervation, fasting, aging, and various diseases. Although the underlying molecular mechanisms are still not fully understood, skeletal muscle atrophy is closely associated with reactive oxygen species (ROS) overproduction. In this study, we aimed to investigate the involvement of ROS in skeletal muscle atrophy from the perspective of gene regulation, and further examine therapeutic effects of antioxidants on skeletal muscle atrophy. Microarray data showed that the gene expression of many positive regulators for ROS production were up-regulated and the gene expression of many negative regulators for ROS production were down-regulated in mouse soleus muscle atrophied by denervation (sciatic nerve injury). The ROS level was significantly increased in denervated mouse soleus muscle or fasted C2C12 myotubes that had suffered from fasting (nutrient deprivation). These two muscle samples were then treated with N-acetyl-L-cysteine (NAC, a clinically used antioxidant) or pyrroloquinoline quinone (PQQ, a naturally occurring antioxidant), respectively. As compared to non-treatment, both NAC and PQQ treatment (1) reversed the increase in the ROS level in two muscle samples; (2) attenuated the reduction in the cross-sectional area (CSA) of denervated mouse muscle or in the diameter of fasted C2C12 myotube; (3) increased the myosin heavy chain (MHC) level and decreased the muscle atrophy F-box (MAFbx) and muscle-specific RING finger-1 (MuRF-1) levels in two muscle samples. Collectively, these results suggested that an increased ROS level was, at least partly, responsible for denervation- or fasting-induced skeletal muscle atrophy, and antioxidants might resist the atrophic effect via ROS-related mechanisms.
Highlights
Skeletal muscle is a very important organ in the body and maintains many important functions, such as locomotion, metabolism, and respiration
Among a number of later works, our observations showed that skeletal denervation- or drug-induced skeletal muscle atrophy led to significant up-regulation of muscle RING finger-1 (MuRF1) and muscle atrophy F-box (MAFbx) (Sun et al, 2014a,b; He et al, 2016), while other researchers found that MuRF1 and MAFbx were up-regulated in skeletal muscle atrophy associated with cancer cachexia and cerebral ischemia (Gomes et al, 2012; Desgeorges et al, 2015; Winbanks et al, 2016)
In this study we aimed to investigate the involvement of reactive oxygen species (ROS) in skeletal muscle atrophy from the perspective of gene regulation, and further examine the therapeutic effects of antioxidants on skeletal muscle atrophy
Summary
Skeletal muscle is a very important organ in the body and maintains many important functions, such as locomotion, metabolism, and respiration. Muscle RING finger-1 (MuRF1) and muscle atrophy F-box (MAFbx)/atrogin-1 are two musclespecific E3 ubiquitin ligases of the UPS (Bodine and Baehr, 2014; Winbanks et al, 2016). As early as 2001, two pioneering studies reported that MuRF1 and MAFbx genes were altered in disparate muscle atrophy conditions (Bodine et al, 2001; Gomes et al, 2001). Among a number of later works, our observations showed that skeletal denervation- or drug-induced skeletal muscle atrophy led to significant up-regulation of MuRF1 and MAFbx (Sun et al, 2014a,b; He et al, 2016), while other researchers found that MuRF1 and MAFbx were up-regulated in skeletal muscle atrophy associated with cancer cachexia and cerebral ischemia (Gomes et al, 2012; Desgeorges et al, 2015; Winbanks et al, 2016)
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