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.
Pharmacogenomics of Chemically Distinct Classes of Keap1-Nrf2 Activators Identify Common and Unique Gene, Protein, and Pathway Responses In Vivo.
Sex, Age, Specimen part
View SamplesYeast transcription factor Yap1 mediates adaptive response against H2O2 and the cystein thiol reactive Michael acceptor, N-ethylmaleimid (NEM) and acrolein. The response against H2O2 was found to be distinct from that against NEM and acrolein.
Yap1 activation by H2O2 or thiol-reactive chemicals elicits distinct adaptive gene responses.
Treatment
View SamplesCombining genome-wide microarray and functional analyses, we found that EGFR activation abrogates barrier function, increasing transepidermal water loss (TEWL) and transepithelial permeability of water-soluble ions and higher molecular weight dextrans, in part by disrupting the expression of tight junction proteins. EGF decreases certain lipid matrix free fatty acids and ceramides by its actions to repress the expression of specific biosynthetic enzymes.
EGFR regulation of epidermal barrier function.
Specimen part
View SamplesTCDD increased expression of numerous differentiation specific genes and decreased expression of numerous genes involved in mitochondrial health and redox homeostasis
2,3,7,8-Tetrachlorodibenzo-p-dioxin-mediated production of reactive oxygen species is an essential step in the mechanism of action to accelerate human keratinocyte differentiation.
Specimen part, Cell line
View SamplesThe activities of the dithiolethione analogs, D3T, OLT, and TBD are pharmacologically well-understood. These compounds act as chemopreventive agents whose ability is to block or diminish early stages of carcinogenesis. In addition, the three compounds are classified as monofunctional Phase II enzyme inducers and activate the same pathway, namely the Keap1-Nrf2 signal pathway. The three dithiolethiones were showed to ameliorate the AFB1-induced toxicity through increasing phase II enzymes including glutathione S-transferase (GST). The parent D3T was observed to be the most potent chemoprotective agent. Oltipraz, a clinically approved drug, has been shown to exhibit less efficacy than its analogs for inhibition of aflatoxin-induced hepatic foci.TBD was suggested to be better than OLT as a chemopreventive agent because of its reduced toxicity profile.
Chemical genomics of cancer chemopreventive dithiolethiones.
No sample metadata fields
View SamplesTwo azide mutagenized lines Freeze Resistance (FR, 75% survival) and Freeze Susceptible (FS, 30% survival) were compared with and without 4C 1.5 cold acclimation of crown tissue to identify genes responsible for the difference in freeze resistance.
Cbf genes of the Fr-A2 allele are differentially regulated between long-term cold acclimated crown tissue of freeze-resistant and - susceptible, winter wheat mutant lines.
No sample metadata fields
View SamplesThe cell surface mucin MUC1 is an important host factor limiting Helicobacter pylori (H. pylori) pathogenesis in both humans and mice by providing a protective barrier and modulating mucosal epithelial and leukocyte responses.
Influence of the MUC1 Cell Surface Mucin on Gastric Mucosal Gene Expression Profiles in Response to <i>Helicobacter pylori</i> Infection in Mice.
Time
View SamplesOur understanding of the mechanisms that govern the cellular process of meiosis is limited in higher plants with polyploid genomes. Bread wheat is an allohexaploid that behaves as a diploid during meiosis. Chromosome pairing is restricted to homologous chromosomes despite the presence of homoeologues in the nucleus. The importance of wheat as a crop and the extensive use of wild wheat relatives in breeding programs has prompted many years of cytogenetic and genetic research to develop an understanding of the control of chromosome pairing and recombination. The rapid advance of biochemical and molecular information on meiosis in model organisms such as yeast provides new opportunities to investigate the molecular basis of chromosome pairing control in wheat. However, building the link between the model and wheat requires points of data contact. We report here a large-scale transcriptomics study using the Affymetrix wheat GeneChip aimed at providing this link between wheat and model systems and at identifying early meiotic genes. Analysis of the microarray data identified 1,350 transcripts temporally-regulated during the early stages of meiosis. Expression profiles with annotated transcript functions including chromatin condensation, synaptonemal complex formation,recombination and fertility were identified. From the 1,350 transcripts, 30 displayed at least an eight-fold expression change between and including pre-meiosis and telophase II, with more than 50% of these having no similarities to known sequences in NCBI and TIGR databases. This resource is now available to support research into the molecular basis of pairing and recombination control in the complex polyploid, wheat.
Microarray expression analysis of meiosis and microsporogenesis in hexaploid bread wheat.
Specimen part
View SamplesS-adenosylmethionine (SAM) is the methyl donor for biological methylation modifications that regulate protein and nucleic acid functions. Here we show that methylation of a phospholipid, phosphatidylethanolamine (PE), is the major consumer of SAM in budding yeast. The induction of phospholipid biosynthetic genes is accompanied by induction of the enzyme that hydrolyzes S-adenosylhomocysteine (SAH), a product and inhibitor of methyltransferases. Beyond its function for the synthesis of phosphatidylcholine (PC), the methylation of PE facilitates the turnover of SAM for the synthesis of cysteine and glutathione. Strikingly, cells that lack PE methylation accumulate SAM, which leads to hypermethylation of histones and the major phosphatase PP2A, dependency on cysteine, and sensitivity to oxidative stress. Without PE methylation, particular sites on histones then become methyl sinks to enable the turnover of SAM. These findings reveal an unforeseen metabolic function for phospholipid and histone methylation intrinsic to the life of a cell. Overall design: Two biological replicates of wild type and cho2? cells in YPL media, in SL media after 1 hour and in SL media after 3 hour were collected for sequencing.
A Metabolic Function for Phospholipid and Histone Methylation.
Cell line, Subject, Time
View SamplesThere still is a lack of specific, early markers for acute pancreatitis.
RCAN1 is a marker of oxidative stress, induced in acute pancreatitis.
No sample metadata fields
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