Dataset Information

DIA proteomic analysis of unstimulated murine bone marrow derived macrophages from WT, Nrf2 KO and Keap1 KD cells

ABSTRACT: Unstimulated murine bone marrow derived macrophages cultured in L92 media from WT (4 biological replicates), Nrf2 KO (3 biological replicates) and Keap1 KD BMDM (3 biological replicates) were processed and analysed utilising DIA (label free) proteomic analysis. The Nrf2 KO mouse (DOI: 10.1006/bbrc.1997.6943 ) and Keap1 KD mouse ( DOI: 10.1128/MCB.01591-09) were previously published as noted.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Bone Marrow Macrophage

SUBMITTER: Alejandro Brenes

LAB HEAD: Simon C. Arthur

PROVIDER: PXD030455 | Pride | 2022-04-01

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	20211013_164050_300_2020_DUN_SA_Mus_musculus_Candida_albicans.sne	Other
	MR-K1-cntr.raw	Raw
	MR-K2-cntr.raw	Raw
	MR-K3-cntr.raw	Raw
	MR-N1-cntr.raw	Raw

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Publications

Nrf2 activation reprograms macrophage intermediary metabolism and suppresses the type I interferon response.

Ryan Dylan G DG Knatko Elena V EV Casey Alva M AM Hukelmann Jens L JL Dayalan Naidu Sharadha S Brenes Alejandro J AJ Ekkunagul Thanapon T Baker Christa C Higgins Maureen M Tronci Laura L Nikitopolou Efterpi E Honda Tadashi T Hartley Richard C RC O'Neill Luke A J LAJ Frezza Christian C Lamond Angus I AI Abramov Andrey Y AY Arthur J Simon C JSC Cantrell Doreen A DA Murphy Michael P MP Dinkova-Kostova Albena T AT

iScience 20220130 2

To overcome oxidative, inflammatory, and metabolic stress, cells have evolved cytoprotective protein networks controlled by nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) and its negative regulator, Kelch-like ECH associated protein 1 (Keap1). Here, using high-resolution mass spectrometry we characterize the proteomes of macrophages with altered Nrf2 status revealing significant differences among the genotypes in metabolism and redox homeostasis, which were validated with respirometry an ...[more]

PMID: 35198887

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Project description:Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that induces a battery of cytoprotective genes in response to oxidative/electrophilic stress. Kelch-like ECH associating protein 1 (Keap1) sequesters Nrf2 in the cytosol. The purpose of this study was to investigate the role of Nrf2 in regulating the mRNA of genes encoding drug metabolizing enzymes and xenobiotic transporters. Microarray analysis was performed in livers of Nrf2-null, wild-type, Keap1-knockdown mice with increased Nrf2 activation, and Keap1-hepatocyte knockout mice with maximum Nrf2 activation. In general, Nrf2 did not have a marked effect on uptake transporters, but the mRNAs of organic anion transporting polypeptide 1a1, sodium taurocholate cotransporting polypeptide, and organic anion transporter 2 were decreased with Nrf2 activation. The effect of Nrf2 on cytochrome P450 (Cyp) genes was minimal, with only Cyp2a5, Cyp2c50, Cyp2c54, and Cyp2g1 increased, and Cyp2u1 decreased with enhanced Nrf2 activation. However, Nrf2 increased mRNA of many other phase-I enzymes, such as aldo-keto reductases, carbonyl reductases, and aldehyde dehydrogenase 1. Many genes involved in phase-II drug metabolism were induced by Nrf2, including glutathione S -transferases, UDP- glucuronosyltransferases, and UDP-glucuronic acid synthesis enzymes. Efflux transporters, such as multidrug resistance-associated proteins, breast cancer resistant protein, as well as ATP-binding cassette g5 and g8 were induced by Nrf2. In conclusion, Nrf2 markedly alters hepatic mRNA of a large number of drug metabolizing enzymes and xenobiotic transporters, and thus Nrf2 plays a central role in xenobiotic metabolism and detoxification. We used microarrays to detail the global programme of gene expression in response to Nrf2 activation and identified distinct classes of up- and down-regulated genes. process. Gene expression in livers of Nrf2-null, WT, Keap1-KD, and Keap1-HKO mice was determined using Affymetrix Mouse 430.20 arrays by the KUMC Microarray Core Facility. Biological cRNA replicates (n=3) of each genotype were hybridized to an individual array.