Skeletal muscle wasting after burn is regulated by a decrease in anabolic signaling in the early flow phase

Abstract

Following burns a sustained catabolic stress response is activated, resulting in skeletal muscle wasting. A better understanding of the underlying mechanisms of postburn skeletal muscle wasting is essential for the development of preventive and/or therapeutic strategies. Six weeks old female rats underwent a sham, 10% or 40% total body surface area scald burn. Ten days post-injury, severely burned animals gained significantly less weight compared to sham treated and minor burned animals, reflected in a significantly lower ratio of muscle to total body weight for Soleus (SOL) and Extensor Digitorum Longus (EDL) in the severely burned group. Postburn, total fiber number was significantly lower in EDL, while in SOL the amount of type1 fibers significantly increased and type2 fibers significantly decreased. No signs of mitochondrial dysfunction (COX/SDH) or apoptosis (caspase-3) were found. In SOL and EDL, eEF2 and pAKT expression was significantly lower after severe burn. MURF1,2,3 and Atrogin-1 was significantly higher in SOL, whilst in EDL MURF1,2,3 was significantly lower postburn. In both muscles, FOXO3A was significantly lower postburn. This study identified postburn changes in muscle anthropomorphology and proteins involved in pathways regulating protein synthesis and breakdown, with more pronounced catabolic effects in SOL.

Keywords: Burns; Muscle wasting; Protein turnover; Signaling pathways; Skeletal muscle.