Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome
Year: 2017
Type: article
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−/− andCyp1a2−/− (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 toCyp1a1−/− and 119 unique toCyp1a2−/− mice. Gene Set Enrichment Analysis revealed pathways including apoptosis, DNA repair and early estrogen response that were differentially regulated between WT,Cyp1a1−/− andCyp1a2−/− 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 ofCyp1a1−/− andCyp1a2−/− mice to HLI and suggest novel pathways that need to be investigated as possible therapeutic targets for acute lung injury.
Source: Scientific Reports
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: Developing Effective Epigenetic Biomarkers to Identify Individuals with High Risk of Cancer, G126196642, G1508127230, G1883723547, G204732049, Role of cytochrome P4501B1 in oxygen-mediated pulmonary injury, Role of hepatic and pulmonary P4501A enzymes in neonatal hyperoxic tissue injury, G3150383285, G3986214232, Functional roles of Nrf2 and NQO1 genetic variants in hyperoxic lung injury-ARDS, G5465708471, Mechanistic roles of Cytochrome P4501A enzymes in hyperoxic lung injury, G681011024, G7523309225, G7837447426, G9000033952, G9000042351, G9000095531, G9000240210, G9000240991, Baylor College of Medicine Cancer Center - Cancer Center Support Grant
OpenAlex ID: W2600230613