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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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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

Effect of a point mutation at Keap1 C151 on hepatic gene expression in mice treated with Bardoxolone Methyl (CDDO-Me)

Project description:To investigate the role of Keap1 C151 for induction of gene expression in mouse liver, comprehensive gene expression profiles were compared in the livers of wild-type, Nrf2 knockout, and mice harboring a point mutation at Keap1 C151 (C151S) treated with either CDDO-Me or vehicle

2023-03-07 | GSE222256 | GEO

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

Poorly differentiated, human liposarcoma LiSa-2 cell line response to the synthetic triterpenoid CDDO

Project description:Analysis of poorly differentiated LiSa-2 liposarcoma (LS) cells treated with the synthetic triterpenoid, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) or DMSO or a combination of CDDO and DMSO for up to 11 days. Synthetic triterpenoids exert a variety of actions, including anti-proliferative and proapoptotic effects, making them potentially useful in cancer therapy. Results provide insight into the pathogenesis of LS. Keywords: disease state analysis, CDDO effect, time course

2009-05-14 | GSE3643 | GEO

Poorly differentiated, human liposarcoma LiSa-2 cell line response to the synthetic triterpenoid CDDO

2010-06-25 | E-GEOD-3643 | 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

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