Neonatal extracellular superoxide dismutase knockout mice increase total superoxide dismutase activity and vegf expression after chronic hyperoxia

Maxwell Mathias*, Joann Taylor, Elizabeth Mendralla, Marta Perez

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 languageEnglish (US)
Article number1236
JournalAntioxidants
Volume10
Issue number8
DOIs
StatePublished - Aug 2021

Keywords

  • Bronchopulmonary dysplasia
  • Extracellular superoxide dismutase
  • Nitric oxide signaling
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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