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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Comparison of expression profiles of WT and Nrf2AY/AY mutant macrophages under electrophilic stress agent

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Masayuki Yamamoto

PROVIDER: E-GEOD-75177 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Unique cistrome defined as CsMBE is strictly required for Nrf2-sMaf heterodimer function in cytoprotection.

Otsuki Akihito A Suzuki Mikiko M Katsuoka Fumiki F Tsuchida Kouhei K Suda Hiromi H Morita Masanobu M Shimizu Ritsuko R Yamamoto Masayuki M

Free radical biology & medicine 20151208

Nrf2-small Maf (sMaf) heterodimer is essential for the inducible expression of cytoprotective genes upon exposure to oxidative and xenobiotic stresses. While the Nrf2-sMaf heterodimer recognizes DNA sequences referred to as the antioxidant/electrophile responsive element (ARE/EpRE), we here define these DNA sequences collectively as CNC-sMaf binding element (CsMBE). In contrast, large and small Maf proteins are able to form homodimers that recognize the Maf recognition element (MARE). CsMBE and ...[more]

PMID: 26677805

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Comparison of expression profiles of WT and Nrf2AY/AY mutant macrophages under electrophilic stress agent [RNA-Seq]

Project description:Nrf2(A502Y) mutant failed to recognize cis-element required for induction of Nrf2 target genes.To examine whether Nrf2(A502Y) supports expression of a distinct gene set from that supported by Nrf2, RNA-Seq analysis was performed. We compared gene expression profiles in peritoneal macrophages from Nrf2+/+ and Nrf2AY/AY mice between basal and DEM (which is an electorophilic stress agent promoting Nrf2 induction)-treated conditions. mRNA profiles of wild type (WT) and Nrf2AY/AY (AY) mutant macrophages under basal and DEM-treated condition were generated by deep sequencing, in triplicate.

2016-01-04 | E-GEOD-75176 | biostudies-arrayexpress

Comparison of expression profiles of WT and Nrf2AY/AY mutant macrophages under electrophilic stress agent [ChIP-Seq]

Project description:Nrf2(A502Y) mutant macrophages Nrf2(AY/AY) macrophages were more susceptible to toxicity of xenobiotics. To confirm preferences of binding sequences of Nrf2 and Nrf2A502Y in vivo, we performed ChIP-Seq analyses using an anti-Nrf2 antibody on the DEM-treated peritoneal macrophages derived from Nrf2+/+ and Nrf2AY/AY mice. Chromatin occupancy of wild type (WT) Nrf2 and Nrf2AY mutant under DEM-treated condition were analyzed by deep sequencing, in triplicate

2016-01-04 | E-GEOD-75175 | biostudies-arrayexpress

Zebrafish embryo response to Diethyl maleate

Project description:We have employed the Zebrafish gene expression microarray (MZH_Zebrafish_16k_v1.0) as a discovery platform to analyze the trancriptome of 108hpf (hours post fertilization) embryos exposed from the 96hpf to 108hpf to 100µM of diethylmaleate (DEM). Four two-color microarray studies for measuring expression levels of zebrafish embryos treated with 100µM of diethylmaleate (DEM) were performed. 8 samples were analyzed in total. Four samples were treated with 0.1% DMSO as a control; four samples were treated with 100 µM of DEM and 0.1% DMSO.

2011-09-23 | E-GEOD-32267 | biostudies-arrayexpress

Transcription profiling by array of mouse HuR deficient bone marrow derived macrophages stimulated with lipopolysaccharide

Project description:HuR Deficient and Control, Bone Marrow Derived Macrophages stimulated with Lipopolysaccharides, from Salmonella enteritidis, 100ng/ml for 0, 2 and 6 hours. RNA from 2.000.000 cells was extracted with the RiboPure kit.

2011-01-01 | E-MEXP-2904 | biostudies-arrayexpress

High expression genes in urethane-induced lung tumor

Project description:We estimated differences of urethane-induced tumors between Nrf2+/+ and Nrf2-/- ICR mouse. To identify Nrf2-regulated genes in tumors, we examined the mRNA expression profile both in tumor and non-tumor tissue of mouse 4 months after urethane administration. We performed microarray analyses using the comparable size of lung tumors (1.0 mm < tumor diameter < 1.5 mm) and intact non-tumor lung tissues derived either from Nrf2+/+ (n=8) or Nrf2–/–mice (n=8) at 16-weeks after urethane(1-g/kg body weight) treatment.

2013-04-16 | E-GEOD-46048 | biostudies-arrayexpress

Nrf2 bindng in C2C12 myotubes

Project description:Nrf2 (NF-E2-related-factor-2) contributes to the maintenance of glucose homeostasis in vivo. Nrf2 suppresses blood glucose levels by protecting pancreatic Î²-cells from oxidative stress and improving peripheral tissue glucose utilization. To elucidate the molecular mechanisms by which Nrf2 contributes to the maintenance of glucose homeostasis, we generated skeletal muscle (SkM)-specific Keap1-knockout (Keap1MuKO) mice that express abundant Nrf2 in SkM and then examined Nrf2-target gene expression in this tissue. In Keap1MuKO mice, blood glucose levels were significantly downregulated, and the levels of glycogen branching enzyme (Gbe1) mRNA, along with those of glycogen branching enzyme (GBE) protein, were significantly upregulated in mouse SkM. Consistent with this result, chemical Nrf2-inducers promoted Gbe1 mRNA expression in both mouse SkM and C2C12 myotubes. Chromatin-immunoprecipitation analysis demonstrated that Nrf2 binds the Gbe1 upstream promoter regions. In Keap1MuKO mice, muscle glycogen content was strongly reduced, and forced GBE expression in C2C12 myotubes promoted glucose uptake. Therefore, our results demonstrate that Nrf2-induction in SkM increases GBE expression and reduces muscle glycogen content, resulting in improved glucose tolerance. Chromatin occupancy of Nrf2 under CDDO-Im-treated condition were generated by deep sequencing, in dupliplicate

2016-04-06 | E-GEOD-78780 | biostudies-arrayexpress

Adrenaline-mediated activation of antibiotic production in Streptomyces highlights catechol as elicitor of specialized metabolism

Project description:Actinobacteria are a rich source of bioactive molecules, and genome sequencing has shown that the vast majority of their biosynthetic potential has yet to be explored. However, many of their biosynthetic gene clusters (BGCs) are poorly expressed in the laboratory, which prevents discovery of their cognate natural products. To exploit their full biosynthetic potential, better understanding of the signals that promote the expression of BGCs is needed. Here, we show that the human stress hormone epinephrine (adrenaline) elicits antibiotic production by Actinobacteria. Catechol was established as the likely eliciting moiety, since similar responses were seen for catechol and for the catechol-containing molecules dopamine and catechin but not for related molecules. Exploration of the catechol-responsive strain Streptomyces sp. MBT84 using mass spectral networking revealed elicitation of a BGC that produces the angucycline glycosides aquayamycin, urdamycinone B and galtamycin C. Heterologous expression of the catechol-cleaving enzymes catechol 1,2-dioxygenase or catechol 2,3 dioxygenase counteracted the eliciting effect of catechol. Thus, for the first time we show the activation of natural product biosynthesis by a human hormone, leading to the identification of the ubiquitous catechol moiety as elicitor of BGCs for siderophores and antibiotics.

2022-01-10 | PXD030484 | Pride

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

Project description: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

2007-12-13 | E-GEOD-867 | biostudies-arrayexpress

Characterization of RA839, a non-covalent small-molecule binder to Keap1 and selective activator of Nrf2 signalling

Project description:The activation of the transcription factor NF-E2-related factor 2 (Nrf2) maintains cellular homeostasis in response to oxidative stress by the regulation of multiple cytoprotective genes. Without stressors the activity of Nrf2 is inhibited by its interaction with the kelch-like ECH-associated protein 1 (Keap1). Here, we describe RA839, a small molecule that binds non-covalently to the Nrf2-interacting kelch domain of Keap1 with a Kd of approximately 6 µM, as demonstrated by X-ray co-crystallization and isothermal titration calorimetry. Whole-genome DNA arrays showed that at 10 µM RA839 significantly regulated 105 genes in bone marrow-derived macrophages. Canonical pathway mapping of these genes revealed an activation of pathways linked with Nrf2 signalling. These pathways were also activated after the activation of Nrf2 by the silencing of Keap1 expression. RA839 regulated only two genes in Nrf2 knockout macrophages. Similar to the activation of Nrf2 by either silencing of Keap1 expression or by the reactive compound CDDO-Me, RA839 prevented the induction of both inducible nitric oxide synthase expression and nitric oxide release in response to lipopolysaccharides in macrophages. In mice RA839 acutely induced Nrf2-target gene expression in liver. RA839 is a selective inhibitor of the Keap1/Nrf2 interaction and a useful tool compound to study the biology of Nrf2. Gene expression profile of bone marrow derived murine macrophages (BMDM) from Nrf2+/+ or Nrf2-/- mice treated with RA838, siKeap1-1 or siKeap1-2 were compared to untreated DMSO control or siControl. Four biological replicates were used for each sample group.

2015-10-31 | E-GEOD-71695 | biostudies-arrayexpress

Allele-specific binding analysis of rs242561 by NRF2 ChIP tagmentation sequencing

Project description:We identified a SNP rs242561, located within a regulatory region of the MAPT gene (encoding microtubule-associated protein Tau). It was consistently occupied by NRF2/sMAF in multiple ChIP-seq experiments, and its strong-binding allele increased transactivation, and accorded higher mRNA levels in cell lines and human brain. To confirm the allele-specific binding, we conducted ChIP tagmentaion sequencing experiment in human lymphoblastoid cell line GM12763 which is heterozygous for rs242561. NRF2 ChIP DNA was isolated from GM12763 cells treated with Sulforaphane (SFN) in triplicates. The region containing rs242561 was amplified using primers, Fwd 5â??-AGCCTTCCCTGTCCTTGATT-3â??, Rev 5â??-GGACCGAGCTTCCAGTCTAA-3â??, and tagmentated using Tn5-based transposition for library construction. Libraries were sequenced on Illumina MiSeq. NRF2 ChIP tagmentation sequencing of a 241bp intron region in MAPT gene using GM12763 treated with sulforaphane

2016-04-14 | E-GEOD-79569 | biostudies-arrayexpress

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