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

Yanhong Wei,Huiping Wang,Xiaoyu Li,Xin Peng,Xia Yan,Jie Zhang,Yunfang Gao,Hui Chang,Shenhui Xu

doi:10.1098/rsob.180068

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.

Highlights

Hibernation is a distinctive strategy implemented by certain mammals to survive under conditions of low environmental temperature and food scarcity during winter and can be characterized by repeated torpor– arousal cycles
The ratios of organ wet weight/body weight showed a significant decrease in the PRE, interbout arousal (IBA), early torpor (ET) and late torpor (LT) groups compared with that in the summer active (SA) group; the ratios recovered to SA levels in all organs after hibernation
The content of H2O2 increased significantly by 29.2% ( p, 0.05) in the PRE group and 55.5% ( p, 0.001) in the LT group compared with the SA group; during the torpor – arousal cycle, the H2O2 content in the LT group was higher than that in the IBA group (38.6%, p, 0.01) and ET group (48.8%, p, 0.001)

Summary

Introduction

Hibernation is a distinctive strategy implemented by certain mammals to survive under conditions of low environmental temperature and food scarcity during winter and can be characterized by repeated torpor– arousal cycles. This succession of entry into torpor, deep torpor, arousal and aroused state is called a hibernation bout. Many physiological functions are significantly suppressed compared with those under normal euthermic conditions; for example, substantial decreases in metabolic rate (1% –5%), declines in body temperature (Tb) to near ambient temperature (as low as 18C –58C), and considerable drops in blood flow, heart rate and oxygen consumption [3 –5]. Initiation of interbout arousal from torpor is accompanied by the rapid recovery of many of these physiological functions, including the return of normal Tb (358C–388C), oxygen consumption and metabolic rate [2,5]; for example, during arousal from torpor in thirteen-lined ground squirrels (Spermophilus tridecemlineatus), oxygen consumption increased by 35-fold in about 2 h as Tb rose from 38C to 318C [4]

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Conclusion