Loss of Cytochrome P450 (CYP)1B1 Mitigates Hyperoxia Response in Adult Mouse Lung by Reprogramming Metabolism and Translation

Authors

Sandra L Grimm
Rachel E Stading
Matthew J Robertson
Tanmay Gandhi
Chenlian Fu
Weiwu Jiang
Guobin Xia
Krithika Lingappan
Cristian Coarfa
Bhagavatula Moorthy

Publication Date

8-1-2023

Journal

Redox Biology

DOI

10.1016/j.redox.2023.102790

PMID

37348155

PMCID

PMC10271936

PubMedCentral® Posted Date

6-16-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Infant, Newborn, Animals, Mice, Hyperoxia, Cytochrome P-450 CYP1A2, Lung Injury, Cytochrome P-450 CYP1A1, Mice, Inbred C57BL, COVID-19, Oxygen, Bronchopulmonary Dysplasia, Mice, Knockout, Lung, Animals, Newborn, Hyperoxia, Cytochrome P450, CYP1B1, Bronchopulmonary dysplasia, Lung, Oxidative stress

Abstract

Oxygen supplementation is life saving for premature infants and for 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 and CYP1A2 protect from, hyperoxic lung injury. In this study we tested the hypothesis that Cyp1b1-null mice would revert hyperoxia-induced transcriptomic changes observed in WT mice at the transcript and pathway level. Wild type (WT) C57BL/6J and Cyp1b1-null mice aged 8-10 weeks were maintained in room air (21% O