Hypoxic challenge of hyperoxic pulmonary artery myocytes increases oxidative stress due to impaired mitochondrial superoxide dismutase activity

In this study, we examined whether a transient hypoxic episode exposes antioxidant defense defects in hyperoxic PA myocytes. PA myocytes of term newborn piglets were cultured in hyperoxia (60% O2) or normoxia (21% O2) for 72 h; cells from both groups were challenged with transient hypoxia (10% O2) for 2 h. We measured NOX activity, SOD activities (fractionated by centrifugation and concavalin A- Sepharose chromatography), total ROS and superoxide generation, 8-isoprostane, and calcium responses to thromboxane mimetic. NOX activity increased in hyperoxic myocytes. Hyperoxia increased SOD1 activity but decreased SOD2 activity. Total ROS were reduced in hyperoxia, and hyperoxia + hypoxia groups. While hyperoxia alone did not alter superoxide content, superoxide increased after a hypoxic challenge of both normoxic and hyperoxic myocytes. Increased 8-isoprostane was seen only in hyperoxic myocytes challenged by transient hypoxia. We conclude that hyperoxic PA myocytes can limit total ROS despite increased NOX activity, but with inhibited SOD2 activity. Transient hypoxia increases superoxide formation; in the face of impaired SOD2, despite induction of SOD1, this oxidative stress causes increased 8-isoprostane generation. This may contribute to the mechanism of pulmonary arterial reactivity in infants with severe lung disease.
Source: Pulmonary Pharmacology and Therapeutics - Category: Respiratory Medicine Source Type: research