title: Does lack ofglutathione peroxidase 1gene expression exacerbate lung injury induced by neonatal hyperoxia in mice?
abstract: Supplemental oxygen (O2) increases the risk of lung injury in preterm infants, owing to an immature antioxidant system. Our objective was to determine whether impairing antioxidant defense by decreasingglutathione peroxidase 1(GPx1) gene expression increases the injurious effects of hyperoxia (Hyp).GPx1+/+andGPx1-/-C57Bl/6J mice were exposed to 21% O2(Air) or 40% O2(Hyp) from birth to postnatal day 7 (P7d); they were euthanized on P7d or maintained in air until adulthood [postnatal day 56 (P56d)] to assess short-term and long-term effects, respectively. We assessed lung architecture, three markers of pulmonary oxidative stress (P7d, P56d), macrophages in lung tissue (P7d), immune cells in bronchoalveolar lavage fluid (BALF; P56d), andGPx1-4andcatalasegene expression in lung tissue (P7d, P56d). On P7d, macrophages were decreased by lack ofGPx1expression and further decreased by hyperoxia.GPx1expression was increased inGPx1+/+Hyp mice and decreased in bothGPx1-/-groups. On P56d, heme oxygenase-1 was increased by hyperoxia whenGPx1was absent. There were significantly more immune cells from Hyp groups than from theGPx1+/+Air group and a greater proportion of lymphocytes inGPx1-/-Hyp mice.GPx1expression was significantly decreased inGPx1-/-mice;GPx2-4andcatalaseexpression was increased inGPx1-/-Hyp mice compared with other groups. Tissue fraction was decreased inGPx1-/-Air mice; bronchiolar smooth muscle was decreased inGPx1-/-mice.GPx1does not clearly exacerbate hyperoxia-induced increases in oxidative stress or lung injury but may alter pulmonary immune function. Increased expression ofGPx2-4andcatalaseinGPx1-/-Hyp mice suggests gene redundancy within the model.
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia; and sheena.bouch@sickkids.ca.
authors.forename: Sheena
authors.initials: S
authors.lastname: Bouch
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia; and.
authors.forename: Megan
authors.initials: M
authors.lastname: O'Reilly
authors.affiliation: Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Judy B
authors.initials: JB
authors.lastname: de Haan
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia; and.
authors.forename: Richard
authors.initials: R
authors.lastname: Harding
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Melbourne, Victoria, Australia; and.
authors.forename: Foula
authors.identifier: 0000-0002-3003-9550
authors.initials: F
authors.lastname: Sozo
mesh_terms: D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D018496:Hyperoxia / Q000201:enzymology* / Q000235:genetics*; D008168:Lung / Q000276:immunology / Q000473:pathology; D055370:Lung Injury / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D000447:Aldehydes; D000975:Antioxidants; C002744:3-nitrotyrosine; D014443:Tyrosine; D005979:Glutathione Peroxidase; D051547:Heme Oxygenase-1; C027576:4-hydroxy-2-nonenal; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
keywords: antioxidant; lung structure; lymphocytes; macrophages; oxidative stress