Loss of cytochrome P450 (CYP)1B1 mitigates hyperoxia response in adult mouse lung by reprogramming metabolism and translation

• DOI: 10.1016/j.redox.2023.102790
• Publication Date: 2023-06-16T09:19:27Z
• Authors: Sandra L. Grimm; Rachel E. Stading; Matthew J. Robertson; Tanmay Gandhi; Chenlian Fu; Weiwu Jiang; Guobin Xia; Krithika Lingappan; Cristian Coarfa; Bhagavatula Moorthy
• Keywords: Hyperoxia; CYP1B1

Oxygen supplementation is life saving for premature infants and COVID-19 patients but can induce long-term pulmonary injury by triggering inflammation, with xenobiotic-metabolizing CYP enzymes playing a critical role. Murine studies showed that CYP1B1 enhances, while CYP1A1 CYP1A2 protect from, hyperoxic lung injury. In this study we tested the hypothesis Cyp1b1-null mice would revert hyperoxia-induced transcriptomic changes observed in WT at transcript pathway level. Wild type (WT) C57BL/6J aged 8–10 weeks were maintained room air (21% O2) or exposed to hyperoxia (>95% 48h. Transcriptomic profiling was conducted using Illumina microarray platform. Hyperoxia exposure led robust gene expression same direction WT, Cyp1a1-, Cyp1a2-, mice, different extents each mouse genotype. At transcriptome level, all Cyp1-null murine models reversed effects. Gene Set Enrichment Analysis identified 118 hyperoxia-affected pathways mitigated only including lipid, glutamate, amino acid metabolism. Cell cycle genes Cdkn1a Ccnd1 induced both O2 compared mice. signatures associated positively bronchopulmonary dysplasia (BPD), which occurs (with supplemental oxygen being one of risk factors), did profile after show partial rescue BPD-associated transcriptome. Our suggests plays pro-oxidant role