Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of livers and spleens from Nrf2 knockout mice and wildtype mice to measure differential gene expression.

ABSTRACT: In situ synthesized oligo arrays, U74Av2, from Affymetrix were used to measure differential gene expression in RNA samples generated from the liver (GSE864) and spleen (GSE865) of Nrf2 knockout and wildtype mice at 5 months of age. This SuperSeries is composed of the following subset Series:; GSE864: Nrf2 Knockout vs. Wildtype mice, liver sample; GSE865: Nrf2 Knockout vs. Wildtype mice, spleen sample

ORGANISM(S): Mus musculus

SUBMITTER: Jiang Li

PROVIDER: E-GEOD-867 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Genetic dissection of systemic autoimmune disease in Nrf2-deficient mice.

Li Jiang J Stein Thor D TD Johnson Jeffrey A JA

Physiological genomics 20040811 3

Systemic lupus erythematosus (SLE) is an autoimmune disorder with immune-complex deposition that affects multiple organs. Previous studies have suggested the involvement of oxidative stress and apoptosis in SLE, but no clear link to etiology has been established. Here we show that mice deficient in a transcription factor responsible for controlling the expression of numerous detoxification and antioxidant genes develop an autoimmune disease with multiple organ pathologies that closely resembles ...[more]

PMID: 15173550

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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.

Dataset Information

Transcription profiling of livers and spleens from Nrf2 knockout mice and wildtype mice to measure differential gene expression.

Publications

Genetic dissection of systemic autoimmune disease in Nrf2-deficient mice.

Similar Datasets

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