Antiproteolytic effects of plasma from hibernating bears: A new approach for muscle wasting therapy?

Background & aims In rodents and humans, inactivity or starvation leads to atrophy of skeletal muscle including a decrease in the number and size of muscle cells and in the myofibrillar protein content. It has previously been described that in overwintering bears the inactivity does not provoke any loss of skeletal muscle cell number or size. Taking all these into account, the aim of this study is to test if hibernating bear plasma has any antiproteolytic effect on incubated rat skeletal muscle. Methods Rat skeletal extensor digitorum longus (EDL) muscles were incubated in the presence of hibernating, non-hibernating and control bear plasma. After that, proteolytic rate was evaluated as levels of tyrosine released to the medium and muscle mRNA content for different proteolytic systems were measured by Northern blot. Results Rat skeletal EDL muscles incubation in the presence of hibernating bear plasma resulted in a 40% decrease of the net proteolytic rate. This inhibition of proteolysis was accompanied by decreases in the expression of both lysosomal (cathepsin B) and ubiquitin-dependent (ubiquitin) proteolytic systems. Conclusions The results suggest that during hibernation the bear is able to produce a powerful proteolytic inhibitor which is released to the circulation and blocks muscle wasting associated with immobilization.