Abstract
Due to the advances in perinatal and neonatal care, preterm infants can survive from 22 weeks of gestation. Following extreme prematurity, mechanical ventilation and supplemental oxygen are employed to sustain life. Though supplemental oxygen therapy is clinically necessary it can cause impaired lung growth and repair due to perturbed energy metabolism. To better understand this, we investigated the role of hyperoxia on bioenergetics in mouse lung epithelial cells (MLE-12) exposed to hyperoxia (95% O2, 5% CO2). As short as 4 hours of hyperoxic exposure caused a reduction in the basal respiration, ATP production, and pyruvate utilization compared to air exposed controls as measured by the seahorse bioanalyzer. In addition, the decreased pyruvate utilization was not associated with altered mRNA levels of glucose transporters and mitochondrial pyruvate carriers, nor changes in glycolysis as measured by the glycolytic rate assay. Interestingly, MLE-12 cells exposed to hyperoxia had significantly increased mRNA and protein levels of UCP-1, a transport and uncoupling protein found in the inner mitochondrial membrane which can export monocarboxylate anions such as pyruvate. Despite this increase in UCP-1 we did not see an expected increase in proton leak. These data suggest that hyperoxia may enhance UCP-1 mediated export of pyruvate outside of the mitochondrial matrix rendering it unavailable for oxidative phosphorylation.
Published Version
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