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Protein translation, proteolysis and autophagy in human skeletal muscle atrophy after spinal cord injury
Author(s) -
Lundell L. S.,
Savikj M.,
Kostovski E.,
Iversen P. O.,
Zierath J. R.,
Krook A.,
Chibalin A. V.,
Widegren U.
Publication year - 2018
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.13051
Subject(s) - autophagy , pi3k/akt/mtor pathway , phosphorylation , spinal cord injury , skeletal muscle , protein kinase b , muscle atrophy , spinal cord , atrophy , protein degradation , medicine , endocrinology , biology , microbiology and biotechnology , signal transduction , neuroscience , biochemistry , apoptosis
Aim Spinal 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. Methods Key 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. Results Several 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 FOXO 1 Ser 256 phosphorylation and FOXO 3 protein, decreased in response to spinal cord injury, coincident with attenuated protein abundance of E3 ubiquitin ligases, Mu RF 1 and MAF bx. S6 protein and Ser 235/236 phosphorylation, as well as 4E‐ BP 1 Thr 37/46 phosphorylation, increased transiently after spinal cord injury, indicating higher levels of protein translation early after injury. Protein abundance of LC 3‐I and LC 3‐ 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. Conclusion Together, 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.