Abstract
Bronchopulmonary dysplasia (BPD) is a common lung disease affecting premature infants that develops after exposure to supplemental oxygen and reactive oxygen intermediates. Extracellular superoxide dismutase (SOD3) is an enzyme that processes superoxide radicals and has been shown to facilitate vascular endothelial growth factor (VEGF) and nitric oxide (NO) signaling in vascular endothelium. We utilized a mouse model of neonatal hyperoxic lung injury and SOD3 knockout (KO) mice to evaluate its function during chronic hyperoxia exposure. Wild-type age-matched neonatal C57Bl/6 (WT) and SOD3−/− (KO) mice were placed in normoxia (21% FiO2, RA) or chronic hyperoxia (75% FiO2, O2 ) within 24 h of birth for 14 days continuously and then euthanized. Lungs were harvested for histologic evaluation, as well as comparison of antioxidant enzyme expression, SOD activity, VEGF expression, and portions of the NO signaling pathway. Surprisingly, KO-O2 mice survived without additional alveolar simplification, microvascular remodeling, or nuclear oxidation when compared to WT-O2 mice. KO-O2 mice had increased total SOD activity and increased VEGF expression when compared to WT-O2 mice. No genotype differences were noted in intracellular antioxidant enzyme expression or the NO signaling pathway. These results demonstrate that SOD3 KO mice can survive prolonged hyperoxia without exacerbation of alveolar or vascular phenotype.
Original language | English (US) |
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Article number | 1236 |
Journal | Antioxidants |
Volume | 10 |
Issue number | 8 |
DOIs | |
State | Published - Aug 2021 |
Funding
Acknowledgments: Histology services were provided by the Northwestern University Mouse Histology and Phenotyping Laboratory, which is supported by NCI CCSG P30 CA060553, awarded to the Robert H. Lurie Comprehensive Cancer Center. Gregory Waypa provided guidance on 8-OHdG immunofluorescence analysis. This research was funded by the National Heart, Lung, and Blood Institute (grant K08HL124295 to M.P.) and the Little Giraffe Foundation Neonatal Research Grant (to M.M.).
Keywords
- Bronchopulmonary dysplasia
- Extracellular superoxide dismutase
- Nitric oxide signaling
- Vascular endothelial growth factor
ASJC Scopus subject areas
- Molecular Biology
- Biochemistry
- Physiology
- Clinical Biochemistry
- Cell Biology