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GSE13044
Mus musculus
59 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Exposure to PFOA during gestation altered the expression of genes related to fatty acid catabolism in both the fetal liver and lung. In the fetal liver, the effects of PFOA were robust and also included genes associated with lipid transport, ketogenesis, glucose metabolism, lipoprotein metabolism, cholesterol biosynthesis, steroid metabolism, bile acid biosynthesis, phospholipid metabolism, retinol metabolism, proteosome activation, and inflammation. These changes are consistent with activation of PPAR alpha. Non-PPAR alpha related changes were suggested as well.
Publication Title
Gene expression profiling in the lung and liver of PFOA-exposed mouse fetuses.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 47 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
PPAR-null and wild-type male mice treated with PFHxS or PFNA
Publication Title
Screening a mouse liver gene expression compendium identifies modulators of the aryl hydrocarbon receptor (AhR).
Sample Metadata Fields
Sex, Specimen part, Compound
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Most of the transcriptional changes induced by PFOS in the fetal mouse liver and lung were related to activation of PPARalpha. When compared to the transcript profiles induced by PFOA (Pubmed ID 17681415), few remarkable differences were found other than up-regulation of Cyp3a genes. Because PFOS and PFOA have been shown to differ in their mode of action in the murine neonate, these data suggest that changes related to PFOS-induced neonatal toxicity may not be evident in the fetal transcriptome at term.
Publication Title
Gene expression profiling in the liver and lung of perfluorooctane sulfonate-exposed mouse fetuses: comparison to changes induced by exposure to perfluorooctanoic acid.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Perfluorooctane sulfonate (PFOS) is a perfluoroalkyl acid (PFAA) and a persistent environmental contaminant found in the tissues of humans and wildlife. Although blood levels of PFOS have begun to decline, health concerns remain because of the long half-life of PFOS in humans. Like other PFAAs, such as perfluorooctanoic acid (PFOA), PFOS is an activator of peroxisome proliferator-activated receptor-alpha (PPAR) and exhibits hepatocarcinogenic potential in rodents. PFOS is also a developmental toxicant in rodents where, unlike PFOA, its mode of action is independent of PPAR. Wild-type (WT) and PPAR-null (Null) mice were dosed with 0, 3, or 10 mg/kg/day PFOS for 7 days. Animals were euthanized, livers weighed, and liver samples collected for histology and preparation of total RNA. Gene profiling was conducted using Affymetrix 430_2 microarrays. In WT mice, PFOS induced changes that were characteristic of PPAR transactivation including regulation of genes associated with lipid metabolism, peroxisome biogenesis, proteasome activation, and inflammation. PPAR-independent changes were indicated in both WT and Null mice by altered expression of genes related to lipid metabolism, inflammation, and xenobiotic metabolism. Such results are similar to prior studies done with PFOA and are consistent with modest activation of the constitutive androstane receptor (CAR) and possibly PPAR and/or PPAR/. Unique treatment-related effects were also found in Null mice including altered expression of genes associated with ribosome biogenesis, oxidative phosphorylation and cholesterol biosynthesis. Of interest was up-regulation of Cyp7a1, a gene which is under the control of various transcription regulators. Hence, in addition to its ability to modestly activate PPAR, PFOS induces a variety of off-target effects as well.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
The purpose of this study was to characterize global gene expression in human airway epithelial cells and identify cellular pathways associated with coarse, fine and ultrafine particulate matter (PM) exposures. Ambient PM was collected in 3 different size fractions from Chapel Hill air, particles were extracted from foam or filter matrices and lyophilized. Human primary airway epithelial cells were exposed to particles at 250g/ml or vehicle control for 6h in culture. Following exposure, RNA was isolated and hybridized to human HG U133A affymetrix chips.
Publication Title
Comparison of gene expression profiles induced by coarse, fine, and ultrafine particulate matter.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Epidemiology studies have linked exposure to pollutant particles to increased cardiovascular mortality and morbidity, however, the mechanism remains unknown. In this study, we hypothesized that the ultrafine fraction of ambient pollutant particles would cause endothelial cells dysfunction. We profiled gene expression of human pulmonary artery endothelial cells (HPAEC) exposed to ultrafine Chapel Hill particles (UFP) (100g/ml) or vehicle for 4h with Affymetrix HG U133 Plus 2.0 chips (N = 4 each). Using an unpaired t-test (p <0.01, 5% false discovery rate) we found 426 unique genes to be differentially expressed with 320 upregulated genes and 106 downregulated genes. Among these genes, we noted upregulation of genes related to coagulation-inflammation circuitry including tissue factor (F3), coagulation factor II receptor-like 2 (F2RL2, PAR3), interleukin (IL)-6 and IL-8. Upregulation of these genes were independently confirmed by RT-PCR and/or protein release. Genes related to the CXC chemokine family that have been implicated in the pathogenesis of vascular disease were upregulated, including MCP-1 (2.60 fold), IL-8 (2.47 fold), CXCL1 (1.41 fold), CXCL2 (1.95 fold), CXCL3 (2.28 fold) and CXCR4 (1.30 fold). In addition, genes related to clotting independent signaling of F3 were also differentially expressed, including FOS, JUN and NFKBIA. Treatment of HPAEC with UFP for 16 hours increased the release of IL6 and IL8 by 1.9-fold and 1.8-fold respectively. Pretreatment of HPAEC with a blocking antibody against F3 attenuated IL6 and IL8 release by 30% and 70% respectively. Thus using gene profiling, we uncovered that UFP may induce vascular endothelial cells to express genes related to clotting and angiogenesis. These results provide a novel hypothesis that PM may cause cardiovascular adverse health effects via induction of tissue factor in vascular endothelial cells which then triggers clotting dependent and independent downstream signaling.
Publication Title
Up-regulation of tissue factor in human pulmonary artery endothelial cells after ultrafine particle exposure.
Sample Metadata Fields
Treatment
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
Zinc is a common metal in most ambient particulate matter (PM), and has been proposed to be a causative component in PM-induced adverse cardiovascular health effects. Zinc is also an essential metal and has the potential to induce many physiological and nonphysiological changes. Most toxicological studies employ high levels of zinc. We hypothesized that subchronic inhalation of environmentally relevant levels of zinc would cause cardiac changes in healthy rats. To address this question, healthy male WKY rats (12 wks age) were exposed via nose only inhalation to filtered air or 10, 30 or 100 ug/m3 of aerosolized Zn in sulfate form, 5 h/d, 3 d/wk for 16 wks. Necropsies occurred 48 h after the last exposure to ensure effects were due to chronic exposure rather than the last exposure. No significant changes were observed in neutrophil or macrophage count, total lavageable cells, or enzyme activity levels (lactate dehydrogenase, n-acetyl ?-D-glucosaminidase, ?-glutamyl transferase) in bronchoalveolar lavage fluid, indicating minimal pulmonary effect. In the heart, cytosolic glutathione peroxidase activity decreased, while mitochondrial ferritin levels increased and succinate dehydrogenase activity decreased, suggesting a mitochondria-specific effect. Although no cardiac pathology was seen, cardiac gene array analysis indicated changes in genes involved in cell signaling, a pattern concordant with known zinc effects. These data indicate that inhalation of zinc at environmentally relevant levels may induce cardiac effects. While changes are small in healthy rats, these may be especially relevant in individuals with pre-existent cardiovascular disease.
Publication Title
Subchronic inhalation of zinc sulfate induces cardiac changes in healthy rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR) regulates responses to chemical or physical stress in part by altering expression of genes involved in proteome maintenance. Many of these genes are also transcriptionally regulated by heat shock (HS) through activation by HS factor-1 (HSF1). We hypothesized that there are interactions on a genetic level between PPAR and the HS response mediated by HSF1. Wild-type and PPAR-null mice were exposed to HS, the PPAR agonist WY-14,643 (WY), or both; gene and protein expression was examined in the livers of the mice 4 or 24 hrs after HS. Gene expression profiling identified a number of Hsp family members that were altered similarly in both mouse strains. However, most of the targets of HS did not overlap between strains. A subset of genes was shown by microarray and RT-PCR to be regulated by HS in a PPAR-dependent manner. HS also down-regulated a large set of mitochondrial genes specifically in PPAR-null mice that are known targets of PPARg co-activator 1 (PGC-1) family members. Pretreatment of PPAR-null mice with WY increased expression of PGC-1b and target genes and prevented the down-regulation of the mitochondrial genes by HS. A comparison of HS genes regulated in our dataset with those identified in wild-type and HSF1-null mouse embryonic fibroblasts indicated that although many HS genes are regulated independently of both PPAR and HSF1, a number require both factors for HS responsiveness. These findings demonstrate that the PPAR genotype has a dramatic effect on the transcriptional targets of HS and support an expanded role for PPAR in the regulation of proteome maintenance genes after exposure to diverse forms of environmental stress including HS.
Publication Title
Analysis of the heat shock response in mouse liver reveals transcriptional dependence on the nuclear receptor peroxisome proliferator-activated receptor alpha (PPARalpha).
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 36 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 96 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Male and female CD-1 mice were administered dietary Phenobarbital for 2 or 7 days. In-life, enzyme activity, cell proliferation, genomic analysis, and Bench-mark dose modeling was carried out.
Publication Title
Dose-response modeling of early molecular and cellular key events in the CAR-mediated hepatocarcinogenesis pathway.
Sample Metadata Fields
Specimen part
View Samples