The molecular mechanisms underlying sketetal and cardiac muscle remodeling in the hibernating thirteen-lined ground squirrel

Abstract

The thirteen-lined ground squirrel (Ictidomys tridecemlineatus) survives winters by hibernating, whereby body temperature (Tb) cycles between 4ºC during torpor and 37ºC during arousal. Each organ/tissue of the hibernator must make specific adjustments that allow the ground squirrel to maintain or readjust physiological function during hibernation. The remodeling that occurs in skeletal and cardiac muscle is unique to hibernators, and it is fascinating as a natural means of avoiding physiological dysfunction in these tissues. The purpose of this thesis is to evaluate the molecular mechanisms underlying muscle remodeling in both tissues. It was identified that calcium signaling activates the NFAT-calcineurin pathway, leading to increased expression of hypertrophy-promoting targets in both skeletal and cardiac muscle during torpor. In addition, we found that there is differential expression and activity of transcription factors (Foxo, MyoG) and ubiquitin ligases (MAFbx and MURF1) that promote muscle atrophy in the two tissues being studied.iv