Intermittent hypoxia-hyperoxia and oxidative stress in developing human airway smooth muscle

Colleen M. Bartman, Daniel Wasim Awari, Christina M. Pabelick, Y. S. Prakash

Research output: Contribution to journalArticlepeer-review

Abstract

Premature infants are frequently and intermittently administered supplemental oxygen during hypoxic episodes, resulting in cycles of intermittent hypoxia and hyperoxia. The relatively hypoxic in utero environment is important for lung development while hyperoxia during the neonatal period is recognized as detrimental towards the development of diseases such as bronchopulmonary dysplasia and bronchial asthma. Understanding early mechanisms that link hypoxic, hyperoxic, and intermittent hypoxic-hyperoxic exposures to altered airway structure and function are key to developing advanced therapeutic approaches in the clinic. Changes in oxygen availability can be detrimental to cellular function and contribute to oxidative damage. Here, we sought to determine the effect of oxygen on mitochondria in human fetal airway smooth muscle cells exposed to either 5% O2, 21% O2, 40% O2, or cycles of 5% and 40% O2 (intermittent hypoxia-hyperoxia). Reactive oxygen species production, altered mitochondrial morphology, and changes in mitochondrial respiration were assessed in the context of the antioxidant N-acetylcysteine. Our findings show developing airway smooth muscle is differentially responsive to hypoxic, hyperoxic, or intermittent hypoxic-hyperoxic exposure in terms of mitochondrial structure and function. Cycling O2 decreased mitochondrial branching and branch length similar to hypoxia and hyperoxia in the presence of antioxidants. Additionally, hypoxia decreased overall mitochondrial respiration while the addition of antioxidants increased respiration in normoxic and O2-cycling conditions. These studies show the necessity of balancing oxidative damage and antioxidant defense systems in the developing airway.

Original languageEnglish (US)
Article number1400
JournalAntioxidants
Volume10
Issue number9
DOIs
StatePublished - Sep 2021

Keywords

  • Antioxidants
  • Antioxidative damage
  • Asthma
  • Hyperoxic-induced lung injury
  • Intermittent oxygen
  • Lung
  • Lung disease
  • Neonatal
  • Oxidative injury
  • Perinatal
  • Redox signaling

ASJC Scopus subject areas

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

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