Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from rat livers - Naproxen and NO-Naproxen treatment

ABSTRACT: To characterize naproxen and NO-naproxen, their effects on gene expression in livers of treated rats was examined. We have previously worked with liver and could therefore identify a moderate to strong antioxidant response element signature. There were two goals to this study: 1) to determine whether naproxen and NO-naproxen yield similar gene expression profiles, which would imply that their effects are mediated by the parent NSAID, and 2) to determine whether NO-naproxen, due to the release of NO, might cause increases in expression of genes associated with the antioxidant response element (ARE). In this dataset, we include the expression data obtained from liver of untreated rats and rats treated with naproxen (400mg/kg diet) or NO-naproxen (550mg/kg diet) for 7 days. Total 12 samples were analyzed. We generated the following comparisons: NO-Naproxen vs. Control and Naproxen vs. Control. Genes with a p-value < 0.05 and a fold-change M-bM-^IM-%1.5 were selected.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Yan Lu

PROVIDER: E-GEOD-52054 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Examination of three retinoid X receptor (RXR) agonists [Targretin (TRG), UAB30, and 4-methyl-UAB30 (4-Me-UAB30)] showed that all inhibited mammary cancer in rodents and two (TRG and 4-Me-UAB30) strikingly increased serum triglyceride levels. Agents were administered in diets to female Sprague-Dawley rats. Liver RNA was isolated and microarrayed on the Affymetrix GeneChip Rat Exon 1.0 ST array. Statistical tests identified genes that exhibited differential expression and fell into groups, or modules, with differential expression among agonists. Genes in specific modules were changed by one, two, or all three agonists. An interactome analysis assessed the effects on genes that heterodimerize with known nuclear receptors. For proliferator-activated receptor α/RXR-activated genes, the strongest response was TRG > 4-Me-UAB30 > UAB30. Many liver X receptor/RXR-related genes (e.g., Scd-1 and Srebf1, which are associated with increased triglycerides) were highly expressed in TRG and 4-Me-UAB30- but not UAB30-treated livers. Minimal expression changes were associated with retinoic acid receptor or vitamin D receptor heterodimers by any of the agonists. UAB30 unexpectedly and uniquely activated genes associated with the aryl hydrocarbon hydroxylase (Ah) receptor (Cyp1a1, Cyp1a2, Cyp1b1, and Nqo1). Based on the Ah receptor activation, UAB30 was tested for its ability to prevent dimethylbenzanthracene (DMBA)-induced mammary cancers, presumably by inhibiting DMBA activation, and was highly effective. Gene expression changes were determined by reverse transcriptase-polymerase chain reaction in rat livers treated with Targretin for 2.3, 7, and 21 days. These showed similar gene expression changes at all three time points, arguing some steady-state effect. Different patterns of gene expression among the agonists provided insight into molecular differences and allowed one to predict certain physiologic consequences of agonist treatment. Three treatments were administered. Four samples were obtained for each of the 3 treatment groups for a total of 12 treatment samples. Four control samples were analyzed.

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Expression data from rat livers - Naproxen and NO-Naproxen treatment

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