Protein translation, proteolysis and autophagy in human skeletal muscle atrophy after spinal cord injury

AimSpinal cord injury-induced loss of skeletal muscle mass does not progress linearly. In humans, peak muscle loss occurs during the first 6 weeks postinjury, and gradually continues thereafter. The aim of this study was to delineate the regulatory events underlying skeletal muscle atrophy during the first year following spinal cord injury. MethodsKey translational, autophagic and proteolytic proteins were analysed by immunoblotting of human vastus lateralis muscle obtained 1, 3 and 12 months following spinal cord injury. Age-matched able-bodied control subjects were also studied. ResultsSeveral downstream targets of Akt signalling decreased after spinal cord injury in skeletal muscle, without changes in resting Akt Ser(473) and Akt Thr(308) phosphorylation or total Akt protein. Abundance of mTOR protein and mTOR Ser(2448) phosphorylation, as well as FOXO1 Ser(256) phosphorylation and FOXO3 protein, decreased in response to spinal cord injury, coincident with attenuated protein abundance of E3 ubiquitin ligases, MuRF1 and MAFbx. S6 protein and Ser(235/236) phosphorylation, as well as 4E-BP1 Thr(37/46) phosphorylation, increased transiently after spinal cord injury, indicating higher levels of protein translation early after injury. Protein abundance of LC3-I and LC3-II decreased 3 months postinjury as compared with 1 month postinjury, but not compared to able-bodied control subjects, indicating lower levels of autophagy. Proteins regulating proteasomal degradation were stably increased in response to spinal cord injury. ConclusionTogether, these data provide indirect evidence suggesting that protein translation and autophagy transiently increase, while whole proteolysis remains stably higher in skeletal muscle within the first year after spinal cord injury.