title: Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome.
abstract: Hyperoxia contributes to lung injury in experimental animals and diseases such as acute respiratory distress syndrome in humans. Cytochrome P450 (CYP)1A enzymes are protective against hyperoxic lung injury (HLI). The molecular pathways and differences in gene expression that modulate these protective effects remain largely unknown. Our objective was to characterize genotype specific differences in the transcriptome and proteome of acute hyperoxic lung injury using the omics platforms: microarray and Reverse Phase Proteomic Array. Wild type (WT), Cyp1a1-/- and Cyp1a2-/- (8-10 wk, C57BL/6J background) mice were exposed to hyperoxia (FiO2> 0.95) for 48 hours. Comparison of transcriptome changes in hyperoxia-exposed animals (WT versus knock-out) identified 171 genes unique to Cyp1a1-/- and 119 unique to Cyp1a2-/- mice. Gene Set Enrichment Analysis revealed pathways including apoptosis, DNA repair and early estrogen response that were differentially regulated between WT, Cyp1a1-/- and Cyp1a2-/- mice. Candidate genes from these pathways were validated at the mRNA and protein level. Quantification of oxidative DNA adducts with32P-postlabeling also revealed genotype specific differences. These findings provide novel insights into mechanisms behind the differences in susceptibility of Cyp1a1-/- and Cyp1a2-/- mice to HLI and suggest novel pathways that need to be investigated as possible therapeutic targets for acute lung injury.
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA. lingappa@bcm.edu.
authors.forename: Krithika
authors.initials: K
authors.lastname: Lingappan
authors.affiliation: Advanced Technology Cores, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Suman
authors.initials: S
authors.lastname: Maity
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Weiwu
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Lihua
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Xanthi
authors.initials: X
authors.lastname: Couroucli
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.|Interdepartmental Program in Translational Biology and Molecular Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Veith
authors.affiliation: Institute of Biotechnology, Texas A&M University Health Science Center, Houston, Texas, USA.
authors.forename: Guodong
authors.initials: G
authors.lastname: Zhou
authors.affiliation: Advanced Technology Cores, Baylor College of Medicine, Houston, Texas, USA. coarfa@bcm.edu.
authors.forename: Cristian
authors.initials: C
authors.lastname: Coarfa
authors.affiliation: Department of Pediatrics, Section of Neonatology, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
authors.forename: Bhagavatula
authors.initials: B
authors.lastname: Moorthy
mesh_terms: D000483:Alleles; D000818:Animals; D019295:Computational Biology / Q000379:methods; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics* / Q000378:metabolism*; D004260:DNA Repair; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D005838:Genotype; D018496:Hyperoxia / Q000150:complications*; D055370:Lung Injury / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D058977:Molecular Sequence Annotation; D018384:Oxidative Stress; D020543:Proteome; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction; D059467:Transcriptome
chemical_list: D020543:Proteome; D019363:Cytochrome P-450 CYP1A1