Project description:Rat has been treated with different compounds with the purpose of investigating toxicological mechanisms. But toxic and non-toxic compounds has been administered. 3 toxic (ANIT, DMN, NMF) 3 non-tox (Caerulein, dinitrophenol(DNP), Rosiglitazone) in 5-plicates (30 arrays in all) and 9 untreated (control), 39 samples in all. The array data was used to identify genes with biomarker potential for detecting toxic properties of compounds. Keywords: other Rats was treated with different compounds and RNA from liver was extracyed after 48 hours. Microarrays (GeneChip Rat230 version 2) was run on the RNA
Project description:Activation of the pregnane X receptor (NR1I2) by drugs and other xenobiotics stimulates (or suppresses) expression of numerous genes involved in the metabolic elimination of foreign compounds and some toxic endogenous substrates. We used microarray analysis to identify genes whose expression in rat liver was significantly altered by pregnenolone 16alpha-carbonitrile (PCN) treatment. Keywords: a single ip injection of PCN (100 mg/kg), 8 h treatment
Project description:A series of two color gene expression profiles obtained using Agilent 44K expression microarrays was used to examine sex-dependent and growth hormone-dependent differences in gene expression in rat liver. This series is comprised of pools of RNA prepared from untreated male and female rat liver, hypophysectomized (‘Hypox’) male and female rat liver, and from livers of Hypox male rats treated with either a single injection of growth hormone and then killed 30, 60, or 90 min later, or from livers of Hypox male rats treated with two growth hormone injections spaced 3 or 4 hr apart and killed 30 min after the second injection. The pools were paired to generate the following 6 direct microarray comparisons: 1) untreated male liver vs. untreated female liver; 2) Hypox male liver vs. untreated male liver; 3) Hypox female liver vs. untreated female liver; 4) Hypox male liver vs. Hypox female liver; 5) Hypox male liver + 1 growth hormone injection vs. Hypox male liver; and 6) Hypox male liver + 2 growth hormone injections vs. Hypox male liver. A comparison of untreated male liver and untreated female liver liver gene expression profiles showed that of the genes that showed significant expression differences in at least one of the 6 data sets, 25% were sex-specific. Moreover, sex specificity was lost for 88% of the male-specific genes and 94% of the female-specific genes following hypophysectomy. 25-31% of the sex-specific genes whose expression is altered by hypophysectomy responded to short-term growth hormone treatment in hypox male liver. 18-19% of the sex-specific genes whose expression decreased following hypophysectomy were up-regulated after either one or two growth hormone injections. Finally, growth hormone suppressed 24-36% of the sex-specific genes whose expression was up-regulated following hypophysectomy, indicating that growth hormone acts via both positive and negative regulatory mechanisms to establish and maintain the sex specificity of liver gene expression. For full details, see V. Wauthier and D.J. Waxman, Molecular Endocrinology (2008)
Project description:Living organisms are intricate systems with dynamic internal processes. Their RNA, protein, and metabolite levels fluctuate in response to variations in health and environmental conditions. Among these, RNA expression is particularly accessible for comprehensive analysis, thanks to the evolution of high throughput sequencing technologies in recent years. This progress has enabled researchers to identify unique RNA patterns associated with various diseases, as well as to develop predictive and prognostic biomarkers for therapy response. Such cross-sectional studies allow for the identification of differentially expressed genes (DEGs) between groups, but they have limitations. Specifically, they often fail to capture the temporal changes in gene expression following individual perturbations and may lead to significant false discoveries due to inherent noise in RNA sequencing sample preparation and data collection. To address these challenges, our study hypothesized that frequent, longitudinal RNA sequencing (RNAseq) analysis of blood samples could offer a more profound understanding of the temporal dynamics of gene expression in response to drug interventions, while also enhancing the accuracy of identifying genes influenced by these drugs. In this research, we conducted RNAseq on 829 blood samples collected from 84 Sprague-Dawley lab rats. Excluding the control group, each rat was administered one of four different compounds known for liver toxicity: tetracycline, isoniazid, valproate, and carbon tetrachloride. We developed specialized bioinformatics tools to pinpoint genes that exhibit temporal variation in response to these treatments.