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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Comparison of gene expression profiles of wildtype and two lines of Nrf2 knockout rat livers with or without CDDO-Im treatment

ABSTRACT: Whole livers were collected from rats treated with or without CDDO-Im. Total RNA was purified using Sepazol-RNA I Super G. Gene expression was measured in livers.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Keiko Taguchi

PROVIDER: E-GEOD-77377 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Generation of a New Model Rat: Nrf2 Knockout Rats Are Sensitive to Aflatoxin B1 Toxicity.

Taguchi Keiko K Takaku Misaki M Egner Patricia A PA Morita Masanobu M Kaneko Takehito T Mashimo Tomoji T Kensler Thomas W TW Yamamoto Masayuki M

Toxicological sciences : an official journal of the Society of Toxicology 20160412 1

THE TRANSCRIPTION FACTOR NRF2: (NF-E2-related-factor 2) REGULATES A BATTERY OF ANTIOXIDATIVE STRESS-RESPONSE GENES AND DETOXICATION GENES, AND NRF2 KNOCKOUT LINES OF MICE HAVE BEEN CONTRIBUTING CRITICALLY TO THE CLARIFICATION OF ROLES THAT NRF2 PLAYS FOR CELL PROTECTION HOWEVER, THERE ARE APPARENT LIMITATIONS IN USE OF THE MOUSE MODELS FOR INSTANCE, RATS EXHIBIT MORE SUITABLE FEATURES FOR TOXICOLOGICAL OR PHYSIOLOGICAL EXAMINATIONS THAN MICE IN THIS STUDY, WE GENERATED 2 LINES OF NRF2 KNOCKOUT R ...[more]

PMID: 27071940

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Transcription profiling of mouse Keap1-null (CKO) to investigate genetic and pharmacologic activation of Nrf2 signaling

Project description:Genetic versus chemoprotective activation of Nrf2 signaling: overlapping yet distinct hepatic gene expression profiles between Keap1 knockout and triterpenoid treated mice; Loss of Nrf2 signaling increases susceptibility to acute toxicity, inflammation, and carcinogenesis in mice due to the inability to mount adaptive responses. By contrast, disruption of Keap1 (a cytoplasmic modifier of Nrf2 turnover) protects against these stresses in mice; although dominant negative mutations in Keap1 have been identified recently in some human cancers. Global characterization of Nrf2 activation is important to exploit this pathway for chemoprevention in healthy, yet at-risk individuals and also to elucidate the consequences of hijacking the pathway in Keap1-mutant human cancers. This analysis also enables a global characterization of the pharmacodynamic action of CDDO-Im at a low dose that is relevant to chemoprevention. Experiment Overall Design: Liver-targeted conditional Keap1-null (CKO) mice provide a model of genetic activation of Nrf2 signaling. By coupling global gene expression analysis of CKO mice with analysis of pharmacologic activation using the synthetic oleanane triterpenoid CDDO-Im, we are able to gain insight into pathways affected by Nrf2 activation. CDDO-Im is an extremely potent activator of Nrf2 signaling. CKO mice were used to identify genes modulated by genetic activation of Nrf2 signaling. The CKO response was compared to hepatic global gene expression changes in wild-type mice treated with CDDO-Im at a maximal Nrf2 activating dose. n=3/group, male 9 week old mice were used. Mice were treated with a single dose of vehicle (10% Cremophor-EL, 10% DMSO, and PBS) or 30 umol CDDO-Im/kg body weight by gavage and sacrificed 6 h later.

2009-05-11 | E-GEOD-15633 | biostudies-arrayexpress

Comparison of gene expression profiles of wildtype and two lines of Nrf2 knockout rat livers with or without CDDO-Im treatment

Project description:Whole livers were collected from rats treated with or without CDDO-Im. Total RNA was purified using Sepazol-RNA I Super G.

2016-08-10 | GSE77377 | GEO

Transcriptome Kinetics of 1[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole (CDDO-Im) in Human Umbilical Vein Endothelial Cells (HUVEC): Mechanism of Action of Cytoprotection

Project description:This study evaluated temporal gene expression profiles to better characterize the early transcriptional events and their relationship to the dynamics of the cytoprotective response in human umbilical vein endothelial cells (HUVEC) to CDDO-. Time-course gene expression profiling was performed on HUVEC treated with CDDO-Im for 0.5, 1, 3, 6, and 24 hours.

2015-08-01 | E-GEOD-71622 | biostudies-arrayexpress

Expression profiling by array in livers of Nrf2 null mice administered CDDO-IM

Project description:Nrf2 null mice administered CDDO-IM Nrf2 null mice treated with CDDO-IM

2014-02-18 | E-GEOD-55003 | biostudies-arrayexpress

Expression profiling by array in livers of Nrf2 null mice administered CDDO-IM

Project description:Nrf2 null mice administered CDDO-IM

2014-02-18 | GSE55003 | GEO

Effect of CDDO-2P-Im Treatment in DIPG Cells

Project description:SF8628 Cells were treated with various concentrations of CDDO-2P-Im for 6 hours and then RNA was extracted for gene expression changes

2023-04-20 | GSE228434 | GEO

Effect of CDDO-2P-Im Treatment in Myeloma Cells

Project description:RPMI8226 Cells were treated with various concentrations of CDDO-2P-Im for 6 hours and then RNA was extracted for gene expression changes

2023-03-19 | GSE221526 | GEO

Effect of CDDO-2P-Im Treatment in Ovarian Cells

Project description:OVCAR-8 Cells were treated with various concentrations of CDDO-2P-Im for 6 hours and then RNA was extracted for gene expression changes

2023-04-20 | GSE229652 | GEO

Effect of CDDO-2P-Im Treatment in Fibroblast Cells

Project description:Primary Dermal Fibroblasts (PDF) were treated with various concentrations of CDDO-2P-Im for 6 hours and then RNA was extracted for gene expression changes

2023-04-20 | GSE229704 | GEO

Pharmacogenomic comparison between D3T- and CDDO-Im in mouse liver tissue

Project description:The Keap1/Nrf2 signaling pathway is a tractable target for the pharmacological prevention of tumorigenesis. 3H-1,2-dithiole-3-thione (D3T) and 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole (CDDO-Im) are representative members of two classes of Nrf2-activating chemopreventive agents. Natural dithiolethiones have been widely used in clinical trials for cancer chemoprevention. Synthetic triterpenoids, however, have been shown to be significantly more potent Nrf2 activators and are under clinical evaluation for the treatment of chronic kidney disease. This study seeks to characterize the structure-activity relationship between D3T and CDDO-Im in mouse liver tissue. To this end we treated Wt and Nrf2-null mice with 300 umol/kg bw D3T and 3, 10, and 30 umol/kg bw CDDO-Im every other day for 5 days and evaulated global gene expression changes as a product of both treamtent and genotype using Affymetrix microarray.

2018-02-25 | GSE99199 | GEO

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