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Isolation of Pulmonary Artery Smooth Muscle Cells from Neonatal Mice
Published on: October 19, 2013
Role of ROS, Soluble Guanylate Cyclase and cGMP in Mouse Lung Development During Hyperoxia
My Linh Nguyen1, Joann M Taylor1, V Joseph Dudley1
1Division of Neonatology, Department of Pediatrics, Northwestern University, Feinberg School of Medicine, Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL USA.
Summary
Supplemental oxygen induces reactive oxygen species (ROS) impairing newborn lung development. Cytosolic ROS disrupt cGMP signaling, while mitochondrial ROS hinder alveolarization via independent mechanisms.
Area of Science:
- Biomedical research
- Neonatal physiology
- Cellular biology
Background:
- Bronchopulmonary dysplasia (BPD) involves disrupted lung development in newborns exposed to supplemental oxygen.
- Supplemental oxygen increases reactive oxygen species (ROS), causing cellular damage and contributing to BPD.
- Subcellular ROS localization impacts lung development and cGMP signaling pathways.
Purpose of the Study:
- To investigate the role of subcellular ROS in lung cGMP signaling and development.
- To differentiate the mechanisms of hyperoxia-induced lung injury in distinct subcellular compartments.
- To explore therapeutic targets for preventing BPD-related lung damage.
Main Methods:
- Experiments using HEK293T cells, embryonic lung explants, and neonatal mice exposed to hyperoxia (elevated oxygen).
- Measurement of ROS production in various subcellular compartments (mitochondria, cytosol, intermembrane space).
- Assessment of soluble guanylate cyclase (sGC)-cGMP signaling pathway responsiveness and lung alveolarization.
Main Results:
- Hyperoxia increased mitochondrial ROS in lung explants and HEK293T cells.
- Cytosolic ROS impaired sGC-cGMP signaling, an effect mitigated by ebselen and cinaciguat.
- Mitochondrial ROS mediated hyperoxia-induced impairment of lung alveolar development in neonatal mice, independent of cGMP signaling.
- sGC activators did not rescue hyperoxia-induced lung structural changes.
Conclusions:
- Hyperoxia-induced lung injury involves distinct subcellular mechanisms affecting cGMP signaling and alveolar development.
- Cytosolic ROS impair cGMP signaling, while mitochondrial ROS disrupt lung alveolarization.
- Targeting specific subcellular compartments may offer novel therapeutic strategies for BPD.
