Coping with physiological oxidative stress: a review of antioxidant strategies in seals

Abstract

While diving, seals are exposed to apnea-induced hypoxemia and repetitive cycles of ischemia/reperfusion. While on land, seals experience sleep apnea, as well as prolonged periods of food and water deprivation. Prolonged fasting, sleep apnea, hypoxemia and ischemia/reperfusion increase oxidant production and oxidative stress in terrestrial mammals. In seals, however, neither prolonged fasting nor apnea-induced hypoxemia or ischemia/reperfusion increase systemic or local oxidative damage. The strategies seals evolved to cope with increased oxidant production are reviewed in the present manuscript. Among these strategies, high antioxidant capacity and the oxidant-mediated activation of hormetic responses against hypoxia and oxidative stress are discussed. In addition to expanding our knowledge of the evolution of antioxidant defenses and adaptive responses to oxidative stress, understanding the mechanisms that allow adapted mammals to avoid oxidative damage has the potential to advance our knowledge of oxidative stress-induced pathologies and to enhance the translative value of biomedical therapies in the long term.

Prolonged food deprivation increases mRNA expression of deiodinase 1 and 2, and thyroid hormone receptor β-1 in a fasting-adapted mammal

“…While the role UCP2 plays in regulating cellular metabolism is not well defined, decreased hepatic UCP2 is associated with impaired lipid metabolism and antioxidant capacity in insulin-resistant rats (Montez et al, 2012). Because we have demonstrated that insulin resistance develops with fasting duration in elephant seal pups (Viscarra et al, 2011a;Viscarra et al, 2011b;Viscarra et al, 2012), but with enhanced lipid metabolism and antioxidant capacity (Vázquez-Medina et al, 2011;Vázquez-Medina et al, 2012), the observed increase in UCP2 may contribute to the regulation of both lipid metabolism and oxidative stress in late-fasted pups. Collectively, the increases in the genes measured indicate that fasting duration is associated with upregulation of the TH-mediated signal transduction pathway in adipose and muscle in a select group of mammals uniquely adapted to periods of extensive food deprivation.…”

“…Because our hypothesis focused on the changes in the deiodinases and the TH receptor, these proteins were given priority. Protein expression was quantified by standard western blot as previously described (Vázquez-Medina et al, 2011;Viscarra et al, 2011a;Viscarra et al, 2011b;Vázquez-Medina et al, 2012;Soñanez-Organis et al, 2012;Viscarra et al, 2012). The primary antibodies for DI1 and DI2, THrβ1, TATA binding protein, histone H3 and β-actin (Santa Cruz Biotechnology, Santa Cruz, CA) were diluted 1:500 to 1:5000.…”

“…Tagging of pups at birth helped ensure the accuracy of their age to within 1 or 2 days. Sedation procedures, blood sampling and tissue biopsy collections have been detailed previously (Ortiz et al, 2000;Ortiz et al, 2001;Ortiz et al, 2002;Ortiz et al, 2003;Vázquez-Medina et al, 2011;Viscarra et al, 2011a;Viscarra et al, 2011b;Vázquez-Medina et al, 2012;Viscarra et al, 2012). Biopsies were rinsed with cold, sterile saline, placed in cryogenic vials, immediately frozen by immersion in liquid nitrogen, and stored at −80°C until later analyses.…”

“…Biopsies were rinsed with cold, sterile saline, placed in cryogenic vials, immediately frozen by immersion in liquid nitrogen, and stored at −80°C until later analyses. Frozen tissue samples were homogenized in 500 μl of hypotonic buffer containing a protease and phosphatase inhibitor cocktail (Sigma-Aldrich, St Louis, MO, USA) as previously described (Vázquez-Medina et al, 2011;Viscarra et al, 2011a;Viscarra et al, 2011b;Vázquez-Medina et al, 2012;Viscarra et al, 2012). Nuclear and cytosolic extractions were performed using the Nuclear and Cytoplasmic Extraction Reagents Kit (Thermo Fisher Scientific, Waltham, MA, USA).…”

Characterization of the hypoxia-inducible factor 1 alpha gene in the sperm whale, beluga whale, and Yangtze finless porpoise

“…Diving ability is enhanced by cardiovascular adjustments such as bradycardia (lower heart rate) and peripheral vasoconstriction (Vázquez-Medina et al 2012), while angiogenesis contributes to the maximal oxygen consumption in skeletal muscle capillarity (Gavin et al 2007). Thus, the HIF-1α-induced VEGF expression may contribute to the adaptation of diving species to either aerobic or anaerobic metabolism during breath-hold diving.…”