Autophagy-lysosomal signaling responses to heat stress in tenotomy-induced rat skeletal muscle atrophy.

Abstract Aims The autophagy-lysosomal system plays a crucial role in maintaining muscle proteostasis. Excessive stimulation of the autophagic machinery is a major contributor to muscle atrophy induced by tendon transection. Hyperthermia is known to attenuate muscle protein loss during disuse conditions; however, little is known regarding the response of the autophagy pathway to heat stress following tenotomy-induced muscle atrophy. The purpose of this study was to evaluate whether heat stress would have a beneficial impact on the activation of autophagy in tenotomized soleus and plantaris muscles. Main methods Male Wistar rats were divided into control, control plus heat stress, tenotomy, and tenotomy plus heat stress groups. The effects of tenotomy were evaluated at 8 and 14 days with heat treatment applied using thermal blankets (30 min. day−1, at 40.5–41.5 °C, for 7 days). Key findings Heat stress could normalize tenotomy-induced muscle loss and over-activation of autophagy-lysosomal signaling; this effect was evidently observed in soleus muscle tenotomized for 14 days. The autophagy-related proteins LC3B-II and LC3B-II/I tended to decrease, and lysosomal cathepsin L protein expression was significantly suppressed. While p62/SQSTM1 was not altered in response to intermittent heat exposure in tenotomized soleus muscle at day 14. Phosphorylation of the 4E-BP1 protein was significantly increased in tenotomized plantaris muscle; whereas heat stress had no impact on phosphorylation of Akt and FoxO3a proteins in both tenotomized muscles examined. Significance Our results provide evidence that heat stress associated attenuation of tenotomy-induced muscle atrophy is mediated through limiting over-activation of the autophagy-lysosomal pathway in oxidative and glycolytic muscles.