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1. Nucleic acid damage and DNA repair are affected by freezing stress in annual wheat ( Triticum aestivum ) and by plant age and freezing in its perennial relative ( Thinopyrum intermedium )

   https://doi.org/10.1002/ajb2.1584  

   Jaikumar, Nikhil S. ; Dorn, Kevin M. ; Baas, Dean ; Wilke, Brook ; Kapp, Christian ; Snapp, Sieglinde S. ( December 2020 , American Journal of Botany)

   Nucleic acid integrity can be compromised under many abiotic stresses. To date, however, few studies have considered whether nucleic acid damage and damage repair play a role in cold‐stress adaptation. A further insufficiently explored question concerns how age affects cold stress adaptation among mature perennials. As a plant ages, the optimal trade‐off between growth and stress tolerance may shift.

   Oxidative damage to RNA and expression of genes involved in DNA repair were compared in multiple mature cohorts ofThinopyrum intermedium(an emerging perennial cereal) and in wheat and barley under intermittent freezing stress and under nonfreezing conditions. Activity of glutathione peroxidase (GPX) and four other antioxidative enzymes was also measured under these conditions. DNA repair genes included photolyases involved in repairing ultraviolet‐induced damage and two genes involved in repairing oxidatively induced damage (ERCC1, RAD23).

   Freezing stress was accompanied by large increases in photolyase expression andERCC1expression (in wheat andThinopyrum) and in GPX and GR activity (particularly inThinopyrum). This is the first report of DNA photolyases being overexpressed under freezing stress. OlderThinopyrumhad lower photolyase expression and less freezing‐induced overexpression ofERCC1. YoungerThinopyrumplants sustained more oxidative damage to RNA.

   Overexpression of DNA repair genes is an important aspect of cold acclimation. When comparing adult cohorts, aging was associated with changes in the freezing stress response, but not with overall increases or decreases in stress tolerance.

    

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2. Untangling life span and body mass discrepancies in canids: phylogenetic comparison of oxidative stress in blood from domestic dogs and wild canids

   https://doi.org/10.1152/ajpregu.00067.2020  

   Jimenez, Ana G. ; Downs, Cynthia J. ( August 2020 , American Journal of Physiology-Regulatory, Integrative and Comparative Physiology)

   null (Ed.)

   Canids are a morphological and physiological diverse group of animals, with the most diversity found within one species, the domestic dog. Underlying observed morphological differences, there must also be differences at other levels of organization that could lead to elucidating aging rates and life span disparities between wild and domestic canids. Furthermore, small-breed dogs live significantly longer lives than large-breed dogs, while having higher mass-specific metabolic rates and faster growth rates. At the cellular level, a clear mechanism underlying whole animal traits has not been fully elucidated, although oxidative stress has been implicated as a potential culprit of the disparate life spans of domestic dogs. We used plasma and red blood cells from known aged domestic dogs and wild canids, and measured several oxidative stress variables: total antioxidant capacity (TAC), lipid damage, and enzymatic activities of catalase, superoxide dismutase, and glutathione peroxidase (GPx). We used phylogenetically informed general linear mixed models and nonphylogenetically corrected linear regression analysis. We found that lipid damage increases with age in domestic dogs, whereas TAC increases with age and TAC and GPx activity increases as a function of age/maximum life span in wild canids, which may partly explain longer potential life spans in wolves. As body mass increases, TAC and GPx activity increase in wild canids, but not domestic dogs, highlighting that artificial selection may have decreased antioxidant capacity in domestic dogs. We found that small-breed dogs have significantly higher circulating lipid damage compared with large-breed dogs, concomitant to their high mass-specific metabolism and higher growth rates, but in opposition to their long life spans. 

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3. Thermal preconditioning in a reef-building coral alleviates oxidative damage through a BI-1-mediated antioxidant response

   https://doi.org/10.3389/fmars.2022.971332  

   Majerová, Eva ; Drury, Crawford ( October 2022 , Frontiers in Marine Science)

   Global coral reef decline is largely driven by the breakdown of the coral-algal symbiosis during temperature stress. Corals can acclimatize to higher temperatures, but the cellular processes underlying this ability are poorly understood. We show that preconditioning-based improvements in thermal tolerance in Pocillopora acuta are accompanied by increases in host glutathione reductase (GR) activity and gene expression, which prevents DNA damage. A strong correlation between GR and BI-1 expressions in heat-stressed preconditioned corals and the presence of an antioxidant response element (ARE) in the GR promoter suggest BI-1 could regulate GR expression through Nrf2/ARE pathway. To fortify this link, we developed and GFP-validated an siRNA-mediated gene knockdown protocol and targeted the coral BI-1 gene. BI-1 knock-down specifically decreased GR expression and activity and increased oxidative DNA damage in heat-stressed preconditioned corals, showing that a BI-1-mediated, enhanced antioxidant response during acute heat stress is a key mechanism that prevents oxidative DNA damage after preconditioning. 

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4. Flight and Dietary Antioxidants Influence Antioxidant Expression and Activity in a Migratory Bird

   https://doi.org/10.1093/iob/obab035  

   DeMoranville, Kristen J. ; Carter, Wales A. ; Pierce, Barbara J. ; McWilliams, Scott R. ( December 2021 , Integrative Organismal Biology)

   Ecologically relevant factors such as exercise and diet quality can directly influence how physiological systems work including those involved in maintaining oxidative balance; however, to our knowledge, no studies to date have focused on how such factors directly affect expression of key components of the endogenous antioxidant system (i.e., transcription factors, select antioxidant genes, and corresponding antioxidant enzymes) in several metabolically active tissues of a migratory songbird. We conducted a three-factor experiment that tested the following hypotheses: (H1) Daily flying over several weeks increases the expression of transcription factors NRF2 and PPARs as well as endogenous antioxidant genes (i.e., CAT, SOD1, SOD2, GPX1, GPX4), and upregulates endogenous antioxidant enzyme activities (i.e., CAT, SOD, GPx). (H2) Songbirds fed diets composed of more 18:2n-6 PUFA are more susceptible to oxidative damage and thus upregulate their endogenous antioxidant system compared with when fed diets with less PUFA. (H3) Songbirds fed dietary anthocyanins gain additional antioxidant protection and thus upregulate their endogenous antioxidant system less compared with songbirds not fed anthocyanins. Flight training increased the expression of 3 of the 6 antioxidant genes and transcription factors measured in the liver, consistent with H1, but for only one gene (SOD2) in the pectoralis. Dietary fat quality had no effect on antioxidant pathways (H2), whereas dietary anthocyanins increased the expression of select antioxidant enzymes in the pectoralis, but not in the liver (H3). These tissue-specific differences in response to flying and dietary antioxidants are likely explained by functional differences between tissues as well as fundamental differences in their turnover rates. The consumption of dietary antioxidants along with regular flying enables birds during migration to stimulate the expression of genes involved in antioxidant protection likely through increasing the transcriptional activity of NRF2 and PPARs, and thereby demonstrates for the first time that these relevant ecological factors affect the regulation of key antioxidant pathways in wild birds. What remains to be demonstrated is how the extent of these ecological factors (i.e., intensity or duration of flight, amounts of dietary antioxidants) influences the regulation of these antioxidant pathways and thus oxidative balance.

    

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5. Hypoxia exposure blunts angiogenic signaling and upregulates the antioxidant system in endothelial cells derived from elephant seals

   https://doi.org/10.1186/s12915-024-01892-3  

   Allen, Kaitlin N. ; Torres-Velarde, Julia María ; Vazquez, Juan Manuel ; Moreno-Santillán, Diana D. ; Sudmant, Peter H. ; Vázquez-Medina, José Pablo ( April 2024 , BMC Biology)

   Elephant seals exhibit extreme hypoxemic tolerance derived from repetitive hypoxia/reoxygenation episodes they experience during diving bouts. Real-time assessment of the molecular changes underlying protection against hypoxic injury in seals remains restricted by their at-sea inaccessibility. Hence, we developed a proliferative arterial endothelial cell culture model from elephant seals and used RNA-seq, functional assays, and confocal microscopy to assess the molecular response to prolonged hypoxia.

   Seal and human endothelial cells exposed to 1% O₂for up to 6 h respond differently to acute and prolonged hypoxia. Seal cells decouple stabilization of the hypoxia-sensitive transcriptional regulator HIF-1α from angiogenic signaling. Rapid upregulation of genes involved in glutathione (GSH) metabolism supports the maintenance of GSH pools, and intracellular succinate increases in seal but not human cells. High maximal and spare respiratory capacity in seal cells after hypoxia exposure occurs in concert with increasing mitochondrial branch length and independent from major changes in extracellular acidification rate, suggesting that seal cells recover oxidative metabolism without significant glycolytic dependency after hypoxia exposure.

   We found that the glutathione antioxidant system is upregulated in seal endothelial cells during hypoxia, while this system remains static in comparable human cells. Furthermore, we found that in contrast to human cells, hypoxia exposure rapidly activates HIF-1 in seal cells, but this response is decoupled from the canonical angiogenesis pathway. These results highlight the unique mechanisms that confer extraordinary tolerance to limited oxygen availability in a champion diving mammal.

    

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