Increased Superoxide Dismutase‐2 in skeletal muscle in a rat model of preterm birth

Abstract

BackgroundIn the United States an estimated 12% of births are preterm, meaning a significant number of infants are at increased risk for hypertension, type‐2 diabetes, and insulin resistance later in life. After a preterm birth, a common intervention used is oxygen therapy in order to improve oxygen delivery to systemic tissues. Although acutely life sustaining, there may be adverse effects of oxygen therapy in the long term. Many metabolic alterations have been identified in adults born preterm, including increased risk of insulin resistance and metabolic syndrome. In these conditions, there have been alterations in uncoupling protein‐3 (UCP‐3) expression, a protein that aids in the release of energy from the mitochondria as heat, and superoxide dismutase one and two (SOD‐1 and SOD‐2) expression, which metabolize reactive oxygen species. We hypothesized that altered levels of uncoupling protein and antioxidants would be observed at one year of age in a rat model of prematurity.MethodsWithin 12 hours of their birth, we exposed Harlan Sprague‐Dawley (SD) rat pups for 14 days to either normoxia (NORM, 21% oxygen, n=12, 6 males) or hyperoxia (HYP, 85% oxygen, n=12, 6 males) in custom chambers. After the 14 days, the pups were aged out to one year of age in standard room air. The gastrocnemius muscles were then harvested and flash frozen in liquid nitrogen. Western blotting was used to observe the differences in UCP3, SOD1, and SOD2. Statistics were run by two way ANOVA with Tukey's post hoc analysis.ResultsThere were no differences observed in UCP3 protein expression or SOD1 protein expression (p=0.8). There is a trend towards higher expression of SOD2 expression in HYP rats (p=0.9). There was a trend towards higher expression of SOD2 in the HYP rats compared to NORM rats (38% higher, p=0.08).ConclusionsNo difference in UCP3 expression is indicative that the main mechanism of uncoupling in the skeletal muscle is unaltered, at least in expression, in this rat model of prematurity. SOD1 is the form of SOD present in the cytoplasm, and indicates that there may not be an increased need for antioxidants in the cytoplasm. However, the potentially higher level of SOD2, the mitochondrial form, in HYP rats indicates that there may be increased need for antioxidants in the mitochondria. Previous data has shown altered mitochondrial mass and function in the HYP rats, and this observation of greater expression of SOD2, a potent antioxidant, further supports the possibility of altered mitochondrial function in the HYP rats.Support or Funding InformationNHLBI, R01 HL115061‐03, Suppl (Eldridge) & NHLBI, R01 HL115061 (Eldridge)