Muscle plasticity in hibernating ground squirrels (Spermophilus lateralis) is induced by seasonal, but not low-temperature, mechanisms
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During hibernation, ground squirrels (Spermophilus lateralis) show unusually altered expression of skeletal muscle myosin heavy-chains. Some muscle groups show transitions from fast to slower myosin isoforms despite atrophy, which are not predicted from other mammalian studies of inactivity. We measure myosin protein and mRNA expression, and the mRNA expression of genes important in atrophy and metabolism in a time-course of muscle plasticity prior to, and during extended hibernation. We also investigate the role of strictly low-temperature processes by comparing torpid individuals at 20 and 4°C. Shifts in myosin isoform expression happen at both temperatures, before the onset of torpor, or within the first month of torpor, in all muscles demonstrating isoform remodeling. Skeletal muscle atrophy is greatly attenuated in this hibernating species, and even may be absent in some muscles. When present, atrophy develops early in hibernation, and does not progress in the final 3 months of torpor. Myostatin mRNA is down-regulated 50–75% in the soleus and diaphragm, two important muscles that are spared of atrophy. The transcription factor FOXO1, which spurs proteolytic degradation of contractile proteins through regulation of the ubiquitin ligase MAFbx, is also generally down-regulated, and may contribute to reduced atrophy. Hypoxia-inducible factor (HIF-1α) mRNA expression was reduced 50% in some muscles, while elevated more than 300% in others. Our collective findings most strongly support early, seasonal, phenotype changes in skeletal muscles which are not uniquely confined to, or prompted by, torpor at 4°C. Such seasonal control of myosin would be a novel mechanism in mammalian skeletal muscle, which otherwise is most susceptible to mechanical loading and limb-activity patterns.
KeywordsMyosin heavy-chains Hibernation Skeletal muscle atrophy Myostatin Hypoxia-inducible factor
Funding was provided by NIH Minority Biomedical Research Support of Competitive Research 2 S06 GM063119 (BCR). Expert technical assistance was provided by Akino Higa, Justin Neag, Uyen Pham, Yanett Roman, Lauren Sims, and Karine Vu.
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