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

ABSTRACT: Nrf2 null mice administered CDDO-IM

ORGANISM(S): Mus musculus

PROVIDER: GSE55003 | GEO | 2014/02/18

SECONDARY ACCESSION(S): PRJNA238225

REPOSITORIES: GEO

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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

The NRF2 inducer CDDO-2P-Im provokes a reduction in amyloid beta levels in Alzheimer’s disease model mice

Project description:Alzheimer’s disease (AD) is the most common etiology of dementia. The transcription factor NF-E2-related factor 2 (NRF2) induces the expression of genes encoding phase II detoxification and antioxidant genes. NRF2 is regulated by Kelch-like ECH-associated protein 1 (KEAP1), and the KEAP1-NRF2 system is the key regulatory system involved in cytoprotection. To examine whether pharmacological induction of NRF2 expression alleviates AD phenotypes in vivo, we employed two AD mouse models, i.e., AppNL-G-F/NL-G-F (AppNLGF) and APPV717I::TAUP301L (APP/TAU) mice. As the synthetic oleanane triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11-dien-28-oyl)] (CDDO)-4(-pyridin-2-yl)-imidazole (CDDO-2P-Im) exhibits strong NRF2-inducing activity, in this study, we treated AD model mice with CDDO-2P-Im.

2024-09-09 | GSE271154 | GEO

Comparative gene expression analysis of Nrf2 activators, CDDO-Im, CDDO-Me and dimethyl fumarate (DMF) in VC1 lung cancer cells

Project description:Nrf2 is an important therapeutic target as activation of this pathway detoxifies harmful insults and reduces oxidative stress. However, the role of Nrf2 in cancer biology is controversial. Protection against oxidative stress and inflammation can confer a survival advantage to tumor cells, leading to a poor prognosis, and constitutive activation of Nrf2 has been detected in numerous tumors. In our study, we examined the role of two clinically relevant classes of Nrf2 activators, the synthetic triterpenoids (CDDO-Im and CDDO-Me) and dimethyl fumarate (DMF) in lung cancer. Using microarrays, we attempt to examine whether these Nrf2 activators have an effect on the same subset of Nrf2 genes.

2015-05-31 | GSE65623 | 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

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

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. Gene expression was measured in livers.

2016-08-10 | E-GEOD-77377 | biostudies-arrayexpress

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

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

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