Inhibition of apoptosis by 60% oxygen: a novel pathway contributing to lung injury in neonatal rats.

Yi M, Masood A, Ziino A, Johnson B, Belcastro R, Li J, Shek S, Kantores C, Jankov RP, Tanswell AK. Inhibition of apoptosis by 60% oxygen: a novel pathway contributing to lung injury in neonatal rats. Am J Physiol Lung Cell Mol Physiol 300: L319-L329, 2011. First published December 10, 2010; doi:10.1152/ajplung.00126.2010.-During early postnatal alveolar formation, the lung tissue of rat pups undergoes a physiological remodeling involving apoptosis of distal lung cells. Exposure of neonatal rats to severe hyperoxia (>= 95% O-2) both arrests lung growth and results in increased lung cell apoptosis. In contrast, exposure to moderate hyperoxia (60% O-2) for 14 days does not completely arrest lung cell proliferation and is associated with parenchymal thickening. On the basis of similarities in lung architecture observed following either exposure to 60% O-2, or pharmacological inhibition of physiological apoptosis, we hypothesized that exposure to 60% O-2 would result in an inhibition of physiological lung cell apoptosis. Consistent with this hypothesis, we observed that the parenchymal thickening induced by exposure to 60% O-2 was associated with decreased numbers of apoptotic cells, increased expressions of the antiapoptotic regulator Bcl-xL, and the putative antiapoptotic protein survivin, and decreased expressions of the proapoptotic cleaved caspases-3 and -7. In summary, exposure of the neonatal rat lung to moderate hyperoxia results in an inhibition of physiological apoptosis, which contributes to the parenchymal thickening observed in the resultant lung injury.