Abstract
The effects of heat stress on the morphological properties and intracellular signaling of innervated and denervated soleus muscles were investigated. Heat stress was applied to rats by immersing their hindlimbs in a warm water bath (42°C, 30 min/day, every other day following unilateral denervation) under anesthesia. During 14 days of experimental period, heat stress for a total of seven times promoted growth‐related hypertrophy in sham‐operated muscles and attenuated atrophy in denervated muscles. In denervated muscles, the transcription of ubiquitin ligase, atrogin‐1/muscle atrophy F‐box (Atrogin‐1), and muscle RING‐finger protein‐1 (MuRF‐1), genes was upregulated and ubiquitination of proteins was also increased. Intermittent heat stress inhibited the upregulation of Atrogin‐1, but not MuRF‐1 transcription. And the denervation‐caused reduction in phosphorylated protein kinase B (Akt), 70‐kDa heat‐shock protein (HSP70), and peroxisome proliferator‐activated receptor γ coactivator‐1α (PGC‐1α), which are negative regulators of Atrogin‐1 and MuRF‐1 transcription, was mitigated. In sham‐operated muscles, repeated application of heat stress did not affect Atrogin‐1 and MuRF‐1 transcription, but increased the level of phosphorylated Akt and HSP70, but not PGC‐1α. Furthermore, the phosphorylation of Akt and ribosomal protein S6, which is known to stimulate protein synthesis, was increased immediately after a single heat stress particularly in the sham‐operated muscles. The effect of a heat stress was suppressed in denervated muscles. These results indicated that the beneficial effects of heat stress on the morphological properties of muscles were brought regardless of innervation. However, the responses of intracellular signaling to heat stress were distinct between the innervated and denervated muscles.
Highlights
Skeletal muscles are important tissues for locomotion and metabolic regulation of the body
The activation of the Akt-mammalian target of the rapamycin (mTOR) cascade by heat stress was suppressed in the denervated muscles
Instead, repeated heat stress suppressed the reduction in negative regulators, including phosphorylated Akt, HSP70, and PGC-1a; it inhibited the upregulation of Atrogin-1 transcription in denervated muscles
Summary
Skeletal muscles are important tissues for locomotion and metabolic regulation of the body. Bed rest and spaceflight for humans (Convertino 1990; Ohira et al 2000; Fitts et al 2010) and hindlimb suspension and spaceflight for animals (Desplanches et al 1987; Ohira et al 1992; Sandona et al 2012) were shown to cause muscle mass loss and a shift in fiber phenotype toward a faster type, in antigravity muscles composed predominantly of slow-twitch fibers, such as the soleus (Ohira et al 1992; Fitts et al 2010; Sandona et al 2012) and adductor longus muscles (Riley et al 1996; Ohira et al 2011). Effective countermeasures for denervation-caused muscle atrophy have not been identified
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