Antioxidant defense in the hibernating thirteen-lined ground squirrel, Spermophilus tridecemlineatus.
Dramatic changes in blood flow and oxygen consumption during torpor-arousal cycles could increase the risk of oxidative stress to tissues of mammalian hibernators. Changes to antioxidant defense systems during hibernation were assessed in thirteen-lined ground squirrels, Spermophilus tridecemlineatus, focusing on heme oxygenase 1 (HO1), superoxide dismutase (SOD) and the thioredoxin (Trx) system. Compared with euthermic control squirrels, inducible HO1 was elevated at both the transcriptional and translational level in multiple tissues of hibernating squirrels. The Nrf2/ARE signal transduction pathway commonly regulates HO1 and protein levels of both the transcription factor Nrf2 and its cofactor MafG were elevated in concert with HO1 implicating this pathway in HO1 expression in hibernation. Both cytosolic Cu/Zn SOD and mitochondrial Mn SOD increased significantly in squirrel muscle during hibernation, probably contributing to antioxidant defense during arousal from torpor when oxygen consumption by muscle increases rapidly to support shivering thermogenesis. Proteins of the thioredoxin system (Trx1, Trx2, TrxR2) also rose in multiple tissues during hibernation, perhaps to remedy a glutathione redox imbalance during hibernation. Amino acid sequencing of HO1 and SOD showed strong conservation of sequence compared with nonhibernating mammals but selected substitutions were found that could aid enzyme function at low body temperatures. The data support the idea that hibernators experience oxidative stress over torpor-arousal cycles and in response activate antioxidant defenses to minimize damage. A better understanding of antioxidant defense systems in hibernation may guide the use of antioxidants in medical treatments for ischemia/reperfusion damage and technology for cold preservation of organs.