Paraplegia increases skeletal muscle autophagy.
BACKGROUND
Paraplegia results in significant skeletal muscle atrophy through increases in skeletal muscle protein breakdown. Recent work has identified a novel SIRT1-p53 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 T4-5 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.
Division of Rehabilitation Sciences, University of Texas Medical Branch, Galveston, Texas 77555-1144, USA.
Christopher S
CS
Fry
Micah J
MJ
Drummond
Heidi L
HL
Lujan
Stephen E
SE
DiCarlo
Blake B
BB
Rasmussen
D000818:Animals; D001343:Autophagy / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000294:innervation / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000378:metabolism / Q000473:pathology*; D009434:Neural Pathways / Q000502:physiology; D010264:Paraplegia / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism / Q000473:pathology; D013904:Thoracic Vertebrae / Q000294:innervation
C488368:Sirt1 protein, rat; D056564:Sirtuin 1