Paraplegia increases skeletal muscle autophagy

Abstract

Introduction: 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.

Copyright © 2012 Wiley Periodicals, Inc.

Figures

Figure 1

Whole body and soleus muscle weight. Whole body weight (g) and soleus muscle weight (mg) were measured in the Paraplegia group 10 weeks following complete spinal cord transection and in the Control group. Values are mean ± SE. *Significantly different from control (P < 0.05).

Figure 2

SIRT1 signaling in soleus muscle from Control and Paraplegic rats. Data represent SIRT1 total protein (A), acetylated p53 (Lys379) (B), p53 total protein (C) and phospho-FoxO3a (Ser253) (D). Values are mean ± SE. *Significantly different from control (P < 0.05).

Figure 3

Markers of autophagy induction in soleus muscle from Control and Paraplegic rats. Data represent Atg7 (A), Beclin-1 (B) and LC3B II (C) total protein. Values are mean ± SE. *Significantly different from control (P < 0.05).

Figure 4

MicroRNA expression of miR-9, miR-30a and miR-34a in soleus muscle were measured in the Paraplegia group 10 weeks following complete spinal cord transection and in the Control group. Values are mean ± SE.