title: Inhibition of apoptosis by 60% oxygen: a novel pathway contributing to lung injury in neonatal rats.
abstract: 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.
authors.affiliation: Lung Biology Programme, Physiology and Experimental Medicine, Hospital for Sick Children Research Institute, Toronto, Canada.
authors.forename: Man
authors.initials: M
authors.lastname: Yi
authors.forename: Azhar
authors.initials: A
authors.lastname: Masood
authors.forename: Adrian
authors.initials: A
authors.lastname: Ziino
authors.forename: Ben-Hur
authors.initials: BH
authors.lastname: Johnson
authors.forename: Rosetta
authors.initials: R
authors.lastname: Belcastro
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Samuel
authors.initials: S
authors.lastname: Shek
authors.forename: Crystal
authors.initials: C
authors.lastname: Kantores
authors.forename: Robert P
authors.initials: RP
authors.lastname: Jankov
authors.forename: A Keith
authors.initials: AK
authors.lastname: Tanswell
mesh_terms: D000388:Air; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D005260:Female; D007150:Immunohistochemistry; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced* / Q000473:pathology*; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D019311:Staurosporine / Q000494:pharmacology
chemical_list: D053148:Caspase 3; D019311:Staurosporine; D010100:Oxygen