Antioxidant response to severe hypoxia in Brandt's vole Lasiopodomys brandtii

Abstract

The antioxidant defense system is essential for animals to cope with homeostasis disruption and overcome oxidative stress caused by adverse environmental conditions such as hypoxia. However, our understanding of how this system works in subterranean rodents remains limited. In this study, Brandt's vole Lasiopodomys brandtii was exposed to normoxia (21% O₂ ) or hypoxia (mild or severe hypoxia: 10% or 5% O₂ ) for 6 h. Changes in key enzymes of the classic enzymatic antioxidant system at both mRNA and enzyme activity levels, and tissue antioxidant levels of the low-molecular-weight antioxidant system were determined in brain, liver, and kidney. Transcript levels of the upstream regulator NF-E2-related factor 2 (Nrf2) were also measured. We found that the mRNA expression of Nrf2 and its downstream antioxidant enzyme genes in L. brandtii were relatively conserved in response to hypoxia in most tissues and genes tested, except in the liver. Hepatic Nrf2, Cu/Zn SOD, GPx1, and GPx3 levels were significantly upregulated in response to mild hypoxia, whereas Mn SOD level decreased significantly in severe hypoxia. Unmatched with changes at the RNA level, constitutively high and relatively stable antioxidant enzyme activities were maintained throughout. For the low-molecular-weight antioxidant system, an abrupt increase of cerebral ascorbic acid (AA) levels in hypoxia indicated a tissue-specific antioxidant response. Although hypoxia did not cause significant oxidative damage in most tissues tested, the significant decrease in antioxidant enzyme activities (GPX and GR) and increase in lipid peroxidation in the kidney suggest that prolonged hypoxia may pose a critical threat to this species.

Keywords: Nrf2; climate change; oxidative stress; oxygen fluctuation; subterranean rodent.