Paraplegia increases skeletal muscle autophagy

Introduction: Paraplegia results in significant skeletal muscle atrophy through increases in skeletal muscle protein breakdown. Recent work has identified a novel SIRT1p53 pathway that is capable of regulating autophagy and protein breakdown. Methods: Soleus muscle was collected from 6 male Sprague-Dawley rats 10 weeks after complete T45 spinal cord transection (paraplegia group) and 6 male sham-operated rats (control group). We utilized immunoblotting methods to measure intracellular proteins and quantitative real-time polymerase chain reaction to measure the expression of skeletal muscle microRNAs. Results: SIRT1 protein expression was 37% lower, and p53 acetylation (LYS379) was increased in the paraplegic rats (P < 0.05). Atg7 and Beclin-1, markers of autophagy induction, were elevated in the paraplegia group compared with controls (P < 0.05). Conclusions: Severe muscle atrophy resulting from chronic paraplegia appears to increase skeletal muscle autophagy independent of SIRT1 signaling. We conclude that chronic paraplegia may cause an increase in autophagic cell death and negatively impact skeletal muscle protein balance. Muscle Nerve 46: 793798, 2012