We access the activity-dependent genes in olfactory neuron cells with unilateral naris occlusion model with mouse. Overall design: mRNA profile of olfactory epithelia between closed and open sides of mice naris was compared
Activity-Dependent Gene Expression in the Mammalian Olfactory Epithelium.
Specimen part, Cell line, Subject
View Samples17-estradiol (E2) exerts complex and context-dependent effects in pulmonary hypertension. In hypoxia-induced pulmonary hypertension (HPH), E2 attenuates lung vascular remodeling through estrogen receptor (ER)-dependent effects; however, ER target genes in the hypoxic lung remain unknown. In order to identify the genome regulated by the E2-ER axis in the hypoxic lung, we performed a microarray analysis in lungs from HPH rats treated with E2 (75 mcg/kg/d) ER-antagonist ICI182,780 (3 mg/kg/d). Untreated HPH rats and normoxic rats served as controls. Using a false discovery rate of 10%, we identified a significantly differentially regulated genome in E2-treated vs. untreated hypoxia rats. Genes most up-regulated by E2 encoded matrix metalloproteinase 8, S100 calcium binding protein A8, and IgA Fc receptor; genes most down-regulated by E2 encoded olfactory receptor 63, secreted frizzled-related protein 2, and thrombospondin 2. Several genes affected by E2 changed in the opposite direction after ICI182,780 co-treatment, indicating an ER-regulated genome in HPH lungs. The bone morphogenetic protein antagonist Grem1 (gremlin 1) was up-regulated by hypoxia, but found to be among the most down-regulated genes after E2 treatment. Gremlin 1 protein was reduced in E2-treated vs. untreated hypoxic animals, and ER-blockade abolished the inhibitory effect of E2 on Grem1 mRNA and protein. In conclusion, E2 ER-dependently regulates several genes involved in proliferative and inflammatory processes during hypoxia. Gremlin 1 is a novel target of the E2-ER axis in HPH. Understanding the mechanisms of E2 gene regulation in HPH may allow for selectively harnessing beneficial transcriptional activities of E2 for therapeutic purposes.
Estrogen receptor-dependent attenuation of hypoxia-induced changes in the lung genome of pulmonary hypertension rats.
Treatment
View SamplesThe goal of this study was to identify candidate genes that may influence alcohol consumption by comparing gene expression in 5 brain regions of alcohol-nave iP and P.NP rats.
Candidate genes for alcohol preference identified by expression profiling in alcohol-preferring and -nonpreferring reciprocal congenic rats.
Specimen part
View SamplesA highly significant quantitative trait locus (QTL) that influenced alcohol preference was identified in the iP/iNP rats on chromosome 4.
Identification of candidate genes for alcohol preference by expression profiling of congenic rat strains.
No sample metadata fields
View SamplesStudy of PBMC gene expression during the first 10 weeks of therapy with Pegylated-interferon-alfa2b (PegIntronTM) and ribavirin (administered by weight) in HCV patients.
Cyclic changes in gene expression induced by Peg-interferon alfa-2b plus ribavirin in peripheral blood monocytes (PBMC) of hepatitis C patients during the first 10 weeks of treatment.
Subject
View SamplesThe objective of this study was to determine changes in gene expression within the extended amygdala following binge-like drinking by alcohol-preferring (P) rats. Adult male P rats were given 1-hr access to 15 and 30% ethanol (EtOH) three times daily for 8 weeks. Rats (n = 10/time point for EtOH and n = 6/time point for water) were killed by decapitation 1, 6 and 24 hr after the last drinking episode. Brains were extracted and rapidly frozen in isopentane in dry ice. RNA was prepared from individual micropunch samples of the nucleus accumbens shell (ACB-sh) and central nucleus of the amygada (CeA); microarray analyses were conducted with Affymetrix Rat 230.2 chips. EtOH intakes were 1.5-2 g/kg/session. Because too few genes changed at the individual time points, an overall effect, comparing the water and EtOH groups, was determined. In the ACB-sh and CeA, there were 276 and 402 probe sets for named genes, respectively, that were different between the two groups. There were 1.5- to 3.5- fold more genes up-regulated than down-regulated in both regions, with most differences between 1.1- to 1.2-fold. Although there were several significant Biological Processes categories in common between the 2 regions (e.g., synaptic transmission, neurite development), there were few genes in common between the two regions that differed between the EtOH and water groups. Overall, the results suggest that chronic binge-like alcohol drinking by P rats produces changes in the expression of genes that could alter neuronal function by different mechanisms in the ACB-sh and CeA.
Changes in gene expression in regions of the extended amygdala of alcohol-preferring rats after binge-like alcohol drinking.
Specimen part
View SamplesEthanol exposure during prenatal development causes fetal alcohol spectrum disorder (FASD), the most frequent preventable birth defect and neurodevelopmental disability syndrome. The molecular targets of ethanol toxicity during development are poorly understood. Developmental stages surrounding gastrulation are very sensitive to ethanol exposure. To understand the effects of ethanol on early transcripts during embryogenesis, we treated zebrafish embryos with ethanol during pre-gastrulation period and examined the transcripts by Affymetrix GeneChip microarray before gastrulation. We identified 521 significantly dysregulated genes, including 61 transcription factors in ethanol-exposed embryos. Sox2, the key regulator of pluripotency and early development was significantly reduced. Functional annotation analysis showed enrichment in transcription regulation, embryonic axes patterning, and signaling pathways, including Wnt, Notch and retinoic acid. We identified all potential genomic targets of 25 dysregulated transcription factors and compared their interactions with the ethanol-dysregulated genes. This analysis predicted that Sox2 targeted a large number of ethanol-dysregulated genes. A gene regulatory network analysis showed that many of the dysregulated genes are targeted by multiple transcription factors. Injection of sox2 mRNA partially rescued ethanol-induced gene expression, epiboly and gastrulation defects. Additional studies of this ethanol dysregulated network may identify therapeutic targets that coordinately regulate early development.
Embryonic ethanol exposure alters expression of sox2 and other early transcripts in zebrafish, producing gastrulation defects.
Treatment
View SamplesThe objective of this study was to test the hypothesis that innate differences in gene expression in the brain could
Functional gene expression differences between inbred alcohol-preferring and -non-preferring rats in five brain regions.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis.
Specimen part, Treatment
View SamplesEnvironmental stresses that disrupt protein homeostasis induce phosphorylation of eIF2, triggering repression of global protein synthesis coincident with preferential translation of ATF4, a transcriptional activator of the Integrated stress response (ISR). Depending on the extent of protein disruption, ATF4 may not be able to restore proteostatic control and instead switch to a terminal outcome that features elevated expression of the transcription factor CHOP (GADD153/DDIT3). The focus of this study was to define the mechanisms by which CHOP directs gene regulatory networks that determine cell fate. We find that in response to proteasome inhibition, CHOP induces the expression of a collection of genes encoding transcription regulators, including ATF5, which is preferentially translated during eIF2 phosphorylation. Transcriptional expression of ATF5 is directly activated by both CHOP and ATF4. Knock-down of ATF5 increased cell survival in response to proteasome inhibition, supporting the idea that both ATF5 and CHOP have pro-apoptotic functions. Transcriptome analyses of ATF5-dependent genes revealed targets involved in apoptosis, including, NOXA, which is important for inducing cell death during proteasome inhibition. This study suggests that the ISR features a feed-forward loop of stress induced transcriptional regulators, each subject to transcriptional and translational control that can switch cell fate towards apoptosis.
CHOP induces activating transcription factor 5 (ATF5) to trigger apoptosis in response to perturbations in protein homeostasis.
Specimen part, Treatment
View Samples