Controllable oxidative stress and tissue specificity in major tissues during the torpor–arousal cycle in hibernating Daurian ground squirrels

Abstract

Mammalian hibernators experience repeated hypoxic ischaemia and reperfusion during the torpor–arousal cycle. We investigated levels of oxidative stress, antioxidant capacity, and the underlying mechanism in heart, liver, brain and kidney tissue as well as plasma during different periods of hibernation in Daurian ground squirrels (Spermophilus dauricus). Our data showed that the levels of hydrogen peroxide significantly increased in the heart and brain during late torpor (LT) compared with levels during the summer active (SA) state. The content of malondialdehyde (MDA) was significantly lower during interbout arousal (IBA) and early torpor (ET) than that during SA or pre-hibernation (PRE), and MDA levels in the LT brain were significantly higher than the levels in other states. Superoxide dismutase 2 protein levels increased markedly in the heart throughout the entire torpor–arousal cycle. Catalase expression remained at an elevated level in the liver during the hibernation cycle. Superoxide dismutase 1 and glutathione peroxidase 1 (GPx1) expression increased considerably in all tissues during the IBA and ET states. In addition, the activities of the various antioxidant enzymes were higher in all tissues during IBA and ET than during LT; however, GPx activity in plasma decreased significantly during the hibernation season. The expression of p-Nrf2 decreased in all tissue types during IBA, but significantly increased during LT, especially in liver tissue. Interestingly, most changed indicators recovered to SA or PRE levels in post-hibernation (POST). These results suggest that increased reactive oxygen species during LT may activate the Nrf2/Keap1 antioxidant pathway and may contribute to the decreased MDA levels found during the IBA and ET states, thereby protecting organisms from oxidative damage over the torpor-arousal cycle of hibernation. This is the first report on the remarkable controllability of oxidative stress and tissue specificity in major oxidative tissues of a hibernator.

The H2S–Nrf2–Antioxidant Proteins Axis Protects Renal Tubular Epithelial Cells of the Native Hibernator Syrian Hamster from Reoxygenation-Induced Cell Death

“…Several elements of the H2S-Nrf2-antioxidant proteins axis have been assessed in hibernating species in previous studies [10,23,[33][34][35][36][37]; however, to our knowledge, this is the first time that all the components of this axis were evaluated mechanistically. Additionally, and contrary to previous studies [10,23,[33][34][35][36][37], we assessed the activity and the outcome of the H2S-Nrf2-antioxidant proteins axis in a native hibernator, not under cold anoxia-reoxygenation conditions, but under warm anoxia-reoxygenation conditions, such are the conditions encountered in clinical practice. However, the available data about the protective role of H 2 S in hamster renal cells subjected to cold anoxia-reoxygenation may be proven useful in the field of solid organ transplantation, and more precisely, in graft preservation [10,38].…”

Tissue-specific telomere dynamics in hibernating arctic ground squirrels (Urocitellus parryii)

“…In addition, Orr et al (2009) found that oxidative stress markers in liver did not differ between torpid and aroused arctic ground squirrels, and that oxidative stress was not associated with torpor in several tissues (including liver). In heart tissue, ROS that accumulate during torpor are counteracted by antioxidants released during the subsequent arousal (Wei et al, 2018). Thus, previous work suggests that neither the liver nor heart experiences a significant, enduring ROS load that might shorten telomeres.…”

“…Although there is evidence that both BAT and SM release antioxidants during torpor in European ground squirrels (Spermophilus citellus; Vucetic et al, 2013), ROS production in BAT is higher than that in SM in mice (Mailloux et al, 2011) andrats (Schönfeld andWojtczak, 2012); we presume a similar, tissue-specific ROS pattern is present in hibernating mammals. Additionally, the liver does not experience ROS-mediated oxidative damage during hibernation (Orr et al, 2009;Brown et al, 2012) and ROS production in the heart during late torpor is counteracted by antioxidants in the subsequent arousal episode (Wei et al, 2018). To test whether RTL shortened throughout hibernation, we sampled juvenile females at the middle (early January) and end (mid-March) of their hibernation season.…”

Huddling relieves myocardial glycogen synthesis of Brandt’s voles in mild cold environment

“…All animals were anaesthetized with 50 mg kg -1 sodium pentobarbital between 08:00 and 11:00 on the last day of the experimental period [19,30]. After the rapid removal of cardiac muscle, portions of the ventricles were immediately cut off and fixed in glutaraldehyde.…”