SOD2 activity is not impacted by hyperoxia in murine neonatal pulmonary artery smooth muscle cells and mice

Anita Gupta, Marta Perez, Keng Jin Lee, Joann M. Taylor, Kathryn N. Farrow*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Pulmonary hypertension (PH) complicates bronchopulmonary dysplasia (BPD) in 25% of infants. Superoxide dismutase 2 (SOD2) is an endogenous mitochondrial antioxidant, and overexpression protects against acute lung injury in adult mice. Little is known about SOD2 in neonatal lung disease and PH. C57Bl/6 mice and isogenic SOD2+/ + and SOD2−/ + mice were placed in room air (control) or 75% O2 (chronic hyperoxia, CH) for 14 days. Right ventricular hypertrophy (RVH) was assessed by Fulton’s index. Medial wall thickness (MWT) and alveolar area were assessed on formalin fixed lung sections. Pulmonary artery smooth muscle cells (PASMC) were placed in 21% or 95% O2 for 24 h. Lung and PASMC protein were analyzed for SOD2 expression and activity. Oxidative stress was measured with a mitochondrially-targeted sensor, mitoRoGFP. CH lungs have increased SOD2 expression, but unchanged activity. SOD2−/ + PASMC have decreased expression and activity at baseline, but increased SOD2 expression in hyperoxia. Hyperoxia increased mitochondrial ROS in SOD2+/+ and SOD2−/ + PASMC. SOD2+/+ and SOD2−/ + CH pups induced SOD2 expression, but not activity, and developed equivalent increases in RVH, MWT, and alveolar area. Since SOD2−/ + mice develop equivalent disease, this suggests other antioxidant systems may compensate for partial SOD2 expression and activity in the neonatal period during hyperoxia-induced oxidative stress.

Original languageEnglish (US)
Pages (from-to)6373-6390
Number of pages18
JournalInternational journal of molecular sciences
Volume16
Issue number3
DOIs
StatePublished - Mar 19 2015

Keywords

  • Bronchopulmonary dysplasia
  • Pulmonary hypertension
  • Right ventricular hypertrophy
  • Superoxide dismutase 2 (SOD2)

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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