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...

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Autores principales:	Krithika Lingappan, Suman Maity, Weiwu Jiang, Lihua Wang, Xanthi Couroucli, Alex Veith, Guodong Zhou, Cristian Coarfa, Bhagavatula Moorthy
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/be3f02f52efc4a6089bd1e5a396ef06d
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spelling	oai:doaj.org-article:be3f02f52efc4a6089bd1e5a396ef06d2021-12-02T16:08:20ZRole of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome10.1038/s41598-017-00516-x2045-2322https://doaj.org/article/be3f02f52efc4a6089bd1e5a396ef06d2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00516-xhttps://doaj.org/toc/2045-2322Abstract 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 with 32P-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.Krithika LingappanSuman MaityWeiwu JiangLihua WangXanthi CouroucliAlex VeithGuodong ZhouCristian CoarfaBhagavatula MoorthyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-17 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Krithika Lingappan Suman Maity Weiwu Jiang Lihua Wang Xanthi Couroucli Alex Veith Guodong Zhou Cristian Coarfa Bhagavatula Moorthy Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome
description	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 with 32P-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.
format	article
author	Krithika Lingappan Suman Maity Weiwu Jiang Lihua Wang Xanthi Couroucli Alex Veith Guodong Zhou Cristian Coarfa Bhagavatula Moorthy
author_facet	Krithika Lingappan Suman Maity Weiwu Jiang Lihua Wang Xanthi Couroucli Alex Veith Guodong Zhou Cristian Coarfa Bhagavatula Moorthy
author_sort	Krithika Lingappan
title	Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome
title_short	Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome
title_full	Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome
title_fullStr	Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome
title_full_unstemmed	Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome
title_sort	role of cytochrome p450 (cyp)1a in hyperoxic lung injury: analysis of the transcriptome and proteome
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/be3f02f52efc4a6089bd1e5a396ef06d
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Role of Cytochrome P450 (CYP)1A in Hyperoxic Lung Injury: Analysis of the Transcriptome and Proteome

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