title: Living with stress: regulation of antioxidant defense genes in the subterranean, hypoxia-tolerant mole rat, Spalax.
abstract: Lack of oxygen is life threatening for most mammals. It is therefore of biomedical interest to investigate the adaptive mechanisms which enable mammalian species to tolerate extremely hypoxic conditions. The subterranean mole rat Spalax survives substantially longer periods of hypoxia than the laboratory rat. We hypothesized that genes of the antioxidant defense, detoxifying harmful reactive oxygen species generated during hypoxia and hyperoxia, are involved in Spalax underground adaptation. Using quantitative RT-PCR, we analyzed the mRNA expression levels of seven antioxidant defense genes (catalase, glutathione peroxidase 1, glutathione-S-transferase Pi1, heme oxygenase 1, superoxide dismutase 1 and 2) and a master regulator of this stress pathway, nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in several tissues of two Israeli Spalax species, S. galili (2n=52) and S. judaei (2n=60), and rat. We also studied the differential expression of these genes after experimental hypoxia and hyperoxia as oxidative stress treatments. We found that mRNA levels and transcriptional responses are species and tissue specific. There are constitutively higher transcript levels of antioxidant genes and their transcription factor Nrf2 in Spalax tissue as compared to rat, suggesting an increased ability in the mole rat to withstand hypoxic/hyperoxic insults. In contrast to Spalax, the rat reacts to experimental oxidative stress by changes in gene regulation. In addition, Spalax Nrf2 reveals unique amino acid changes, which may be functionally important for this transcription factor and indicate positive (Darwinian) selection. Antioxidant defense genes are therefore important targets for adaptive change during evolution of hypoxia tolerance in Spalax.
authors.affiliation: Institute of Molecular Genetics, Johannes Gutenberg University, Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Schülke
authors.forename: Daniel
authors.initials: D
authors.lastname: Dreidax
authors.forename: Assaf
authors.initials: A
authors.lastname: Malik
authors.forename: Thorsten
authors.initials: T
authors.lastname: Burmester
authors.forename: Eviatar
authors.initials: E
authors.lastname: Nevo
authors.forename: Mark
authors.initials: M
authors.lastname: Band
authors.forename: Aaron
authors.initials: A
authors.lastname: Avivi
authors.forename: Thomas
authors.initials: T
authors.lastname: Hankeln
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain; D005786:Gene Expression Regulation / Q000235:genetics; D006321:Heart; D018496:Hyperoxia; D000860:Hypoxia / Q000235:genetics*; D008099:Liver; D008969:Molecular Sequence Data; D051267:NF-E2-Related Factor 2 / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D018384:Oxidative Stress / Q000235:genetics / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D016415:Sequence Alignment; D046308:Spalax / Q000235:genetics / Q000502:physiology*; D013045:Species Specificity; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D010100:Oxygen