Proteomic Identification of Seasonally Expressed Proteins Contributing to Heart Function and the Avoidance of Skeletal Muscle Disuse Atrophy in a Hibernating Mammal

Hibernation
in the thirteen-lined ground squirrel (Ictidomys tridecemlineatus) takes place over 4–6
months and is characterized by multiday bouts of hypothermic torpor
(5–7 °C core body temperature) that are regularly interrupted
every 1–2 weeks by brief (12–24 h) normothermic active
periods called interbout arousals. Our goal was to gain insight into
the molecular mechanisms that underlie the hibernator’s ability
to preserve heart function and avoid the deleterious effects of skeletal
muscle disuse atrophy over prolonged periods of inactivity, starvation,
and near-freezing body temperatures. To achieve this goal, we performed
organelle enrichment of heart and skeletal muscle at five seasonal
time points followed by LC-MS-based label-free quantitative proteomics.
In both organs, we saw an increase in the levels of many proteins
as ground squirrels transition from an active state to a prehibernation
state in the fall. Interestingly, seasonal abundance patterns identified
DHRS7C, SRL, TRIM72, RTN2, and MPZ as potential protein candidates
for mitigating disuse atrophy in skeletal muscle, and ex vivo contractile mechanics analysis revealed no deleterious effects in
the ground squirrel’s muscles despite prolonged sedentary activity.
Overall, an increased understanding of protein abundance in hibernators
may enable novel therapeutic strategies to treat muscle disuse atrophy
and heart disease in humans.