The present research aimed to study the interaction of three chemicals, methyl mercury, benzene and trichloroethylene, on mRNA expression alterations in rat liver and kidney measured by microarray analysis. These compounds were selected on presumed different modes of action. The chemicals were administered daily for 14 days at the Lowest-Observed-Adverse-Effect-Level (LOAEL) or at a two- or three-fold lower concentration individually or in binary or ternary mixtures. The compounds had strong antagonistic effects on each others gene expression changes, which included several genes encoding Phase I and II metabolizing enzymes. On the other hand, the mixtures affected the expression of “novel” genes that were not or little affected by the individual compounds. Based on gene expression changes, the three compounds exhibited a synergistic interaction at the LOAEL in the liver and both at the sub-LOAEL and LOAEL in the kidney. Many of the genes induced by mixtures but not by single compounds, such as Id2, Nr2f6, Tnfrsf1a, Ccng1, Mdm2 and Nfkb1 in the liver, are known to affect cellular proliferation, apoptosis and function. This indicates a shift from compound specific response on exposure to individual compounds to a more generic stress response to mixtures. Most of the effects on cell viability as concluded from transcriptomics were not detected by classical toxicological research illustrating the difference in sensitivity of these techniques. These results emphasize the benefit of applying toxicogenomics in mixture interaction studies, which yields biomarkers for joint toxicity and eventually can result in an interaction model for most known toxins.
Transcriptomics analysis of interactive effects of benzene, trichloroethylene and methyl mercury within binary and ternary mixtures on the liver and kidney following subchronic exposure in the rat.
Sex, Age, Specimen part, Treatment, Compound
View SamplesQuercetin has been shown to act as an anti-carcinogen in experimental colorectal cancer (CRC). The aim of the present study was to characterise transcriptome and proteome changes occurring in the distal colon mucosa of rats supplemented with 10 g quercetin/kg diet for 11 weeks. Transcriptome data analysed with Gene Set Enrichment Analysis showed that quercetin significantly downregulated the potentially oncogenic mitogen-activated protein kinase (Mapk) pathway. In addition, quercetin enhanced expression of tumor suppressor genes, including Pten, Tp53 and Msh2, and of cell cycle inhibitors, including Mutyh. Furthermore, dietary quercetin enhanced genes involved in phase I and II metabolism, including Fmo5, Ephx1, Ephx2 and Gpx2. Quercetin increased PPAR target genes, and concomitantly enhanced expression genes in volved in of mitochondrial fatty acid degradation. Proteomics performed in the same samples revealed 33 affected proteins, of which 4 glycolysis enzymes and 3 heatshock proteins were decreased. A proteome-transcriptome comparison showed a low correlation, but both pointed out towards altered energy metabolism.
Transcriptome and proteome profiling of colon mucosa from quercetin fed F344 rats point to tumor preventive mechanisms, increased mitochondrial fatty acid degradation and decreased glycolysis.
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View SamplesThe aim was to investigate mechanisms contributing to quercetins previously described effects on cell-proliferation and -differentiation, which contradicted its proposed anti-carcinogenic potency. In a 10-day experiment, 40 M quercetin stabilized by 1mM ascorbate reduced Caco-2 differentiation up to 50% (P<0.001). Caco-2 RNA from days 5 and 10, hybridized on HG-U133A2.0 Affymetrix GeneChips, showed 1,743 affected genes on both days (P<0.01). All 14 Caco-2 differentiation-associated genes showed decreased expression (P<0.01), including intestinal alkaline phosphatase that was confirmed technically (qRT-PCR) and functionally (enzyme-activity).
Pathway and single gene analyses of inhibited Caco-2 differentiation by ascorbate-stabilized quercetin suggest enhancement of cellular processes associated with development of colon cancer.
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View SamplesGlobal restriction of protein synthesis is a hallmark of cellular stress. Using hydrogen peroxide, we monitor the transcript level and also the translation status for each RNA using cycloheximide to freeze elongating ribosomes. Polyribosome fractionation of cell extracts was used to separate highly translated and poorly translated mRNAs that were then separately analysed.
Global translational responses to oxidative stress impact upon multiple levels of protein synthesis.
Sex, Compound
View SamplesOne common form of translational control is mediated by proteins that bind to the mRNA 5' cap-binding protein eIF4E. These proteins are collectively called 4E binding proteins (4EBPs). Saccharomyces cerevisiae possesses two 4EBPs that are encoded by non-essential genes called CAF20 and EAP1. To determine the impact of gene deletion on gene expression, we monitored the transcript level and also the translation status for each RNA using cycloheximide to freeze elongating ribosomes in wild-type, caf20 and eap1 cells. Polyribosome fractionation of cell extracts was used to separate highly translated and poorly translated mRNAs that were then separately analyzed.
Identifying eIF4E-binding protein translationally-controlled transcripts reveals links to mRNAs bound by specific PUF proteins.
Sex
View SamplesVEGF and VEGFB Play Balancing Roles in Adipose Differentiation, Gene Expression and Function
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Sex, Specimen part, Cell line
View Samplesgene expression study on brain and lung under Dip2a regulation to better understand the role of Dip2a gene during mice brain and lung development.
Large genomic fragment deletions and insertions in mouse using CRISPR/Cas9.
Sex, Specimen part, Cell line
View SamplesCompare m1A levels in the 16S (large) mitochondrial ribosomal RNA in TRMT61B knockdown cells and control.
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Sex, Specimen part
View Sampleswe construct a comprehensive mouse transcriptomic BodyMap across 17 tissues of six-weeks old C57BL/6JJcl mice using RNA-seq. We find different expression patterns between protein-coding and non-coding genes. Liver and adrenal gland expressed the least complex transcriptome, whereas testis and ovary harbor more complex transcriptome than other tissues. We report a comprehensive list of tissue-specific genes across 17 tissues. Our study provides a unique resource of mouse gene-expression profiles, which is helpful for further biomedical research.
No associated publication
Sex, Specimen part, Cell line
View SamplesTo investigate the random X chromosome inactivation in vivo, we used allelic-specific RNA sequencing of single cells in mouse model. The intercross was between two genetically distant strains, C57BL/6 and PWK/Ph.
No associated publication
Sex, Specimen part, Disease, Disease stage, Cell line
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