Project description:Hydroxylated polychlorinated biphenyls are the metabolites produced from polychlorinated biphenyls (PCBs) by drug-metabolizing enzyme cytochrome P450 1A1. These compounds are bound to transthyretin, a major plasma thyroid hormone-binding protein in amphibian tadpoles. The compounds-transthyretin complexes are transferred into the brain across the blood brain barrier in mammals. Thus these compounds are suspected to disrupt neural development in brain. We studied about the effects of hydroxylated PCBs on the thyroid system in brain using metamorphosing tadpoles of African clawed toad, Xenopus laevis. The metamorphosis assay revealed that these compounds had inhibitory effects on the thyroid hormone-induced metamorphosis. This in vivo assay was a powerful tool to detect thyroid-disrupting activities, because we were not able to detect the inhibitory effects of these compounds using thyroid hormone-responsive reporter gene assay in a cultured Xenopus cell line. A genome-wide gene expression analysis in brain following short-term exposure to these compounds demonstrated that the delay of metamorphosis and the morphological thyroid-disrupting changes could be caused partially by disruption of the thyroid hormone-induced gene expression by hydroxylated PCBs. Furthermore, we associated functional ontology terms with the transcripts whose expression were altered by thyroid hormone alone, or thyroid hormone and hydroxylated PCBs. We suggested that these approachs using a technique of bioinformatics revealed molecular mechanism of thyroid-disrupting activities in vivo. Thyroid hormones induce amphibian metamorphosis and alter a lot of thyroid hormone-responsive gene expression. We studied about the effects of hydroxylated PCBs on TH-induced gene expression. Premetamorphic tadpoles were treated with 500 nM hydroxylated PCBs in the presence of 1 nM thyroid hormone for 4 days. After exposure period total RNA was extracted from brain. Study included at least three replicate of each treatment.
Project description:Hydroxylated polychlorinated biphenyls are the metabolites produced from polychlorinated biphenyls (PCBs) by drug-metabolizing enzyme cytochrome P450 1A1. These compounds are bound to transthyretin, a major plasma thyroid hormone-binding protein in amphibian tadpoles. The compounds-transthyretin complexes are transferred into the brain across the blood brain barrier in mammals. Thus these compounds are suspected to disrupt neural development in brain. We studied about the effects of hydroxylated PCBs on the thyroid system in brain using metamorphosing tadpoles of African clawed toad, Xenopus laevis. The metamorphosis assay revealed that these compounds had inhibitory effects on the thyroid hormone-induced metamorphosis. This in vivo assay was a powerful tool to detect thyroid-disrupting activities, because we were not able to detect the inhibitory effects of these compounds using thyroid hormone-responsive reporter gene assay in a cultured Xenopus cell line. A genome-wide gene expression analysis in brain following short-term exposure to these compounds demonstrated that the delay of metamorphosis and the morphological thyroid-disrupting changes could be caused partially by disruption of the thyroid hormone-induced gene expression by hydroxylated PCBs. Furthermore, we associated functional ontology terms with the transcripts whose expression were altered by thyroid hormone alone, or thyroid hormone and hydroxylated PCBs. We suggested that these approachs using a technique of bioinformatics revealed molecular mechanism of thyroid-disrupting activities in vivo.
Project description:Polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that ubiquitously exist in the environment. PCB exposure has been linked to cancer and multi-system toxicity, including neurotoxicity. 2,2',5,5'-Tetrachloro-biphenyl (PCB 52) is one of the most frequently detected congeners in the environment and human blood. The hydroxylated metabolites of PCB 52 may also be neurotoxic, especially for children whose brains are still developing. However, it is challenging to discern the contribution of these metabolites to PCB neurotoxicity because the metabolism of PCB is species-dependent. In this study, we evaluated the subacute neurotoxicity of a human-relevant metabolite, 2,2',5,5'-tetrachlorobiphenyl-4-ol (4-OH-PCB52), on male adolescent Sprague Dawley rats, via a novel polymeric implant drug delivery system grafted subcutaneously, at total loading concentrations ranging from 0%, 1%, 5%, and 10% of the implant (w/w) for 28 days. Y-maze, hole board test, open field test, and elevated plus maze were performed on exposure days 24 to 28 to assess their locomotor activity, and exploratory and anxiety-like behavior. 4-OH-PCB52 and other possible hydroxylated metabolites in serum and vital tissues were quantified using gas chromatography with tandem mass spectrometry (GC-MS/MS). RNA sequencing was performed in striatum and cerebellum. Based on the data including neurobehavior, 4-OH-PCB52 and metabolite levels, gene expression in the striatum and cerebellum; a subacute exposure to 4-OH-PCB52 results in subtle changes in response to exposure.
Project description:Hornyhead turbot (Pleuronichthys verticalis), a sentinel flatfish species, were intraperitoneally injected with environmentally relevant mixtures of polybrominated diphenyl ethers (PBDEs) or polychlorinated biphenyls (PCBs). After 96 h, fish were sacrificed and liver tissue was collected for gene expression analysis using a custom-designed microarray.
Project description:Arabidopsis thaliana is a well-established model system for the analysis of the basic physiological and metabolic pathways of plants. The presented model is a new semi-quantitative mathematical model of the metabolism of Arabidopsis thaliana. The Petri net formalism was used to express the complex reaction system in a mathematically unique manner. To verify the model for correctness and consistency concepts of network decomposition and network reduction such as transition invariants, common transition pairs, and invariant transition pairs were applied. Based on recent knowledge from literature, including the Calvin cycle, glycolysis and citric acid cycle, glyoxylate cycle, urea cycle, sucrose synthesis, and the starch metabolism, the core metabolism of Arabidopsis thaliana was formulated. Each reaction (transition) is experimentally proven. The complete Petri net model consists of 134 metabolites, represented by places, and 243 reactions, represented by transitions. Places and transitions are connected via 572 edges.
Project description:Exposure to Polychlorinated Biphenyls (PCBs) is known to cause serious health effects in human both in pre- and post-natal period. The knowledge of gene expression will help us to develop early disease or disorder biomarkers for PCB induced health effects. We used microarrays to detail the global gene expression profile underlying the effects of high PCB exposure from the cord blood of the PCB-exposed newborn in Slovakia to understand the molecular mechanism of PCB related toxic effect and its functional implications during fetal development.
Project description:To investigate the response of Arabidopsis thaliana plants to non-freezing, cool temperatures, we subjected four week old plants to various chilling temperatures at defined times during the diurnal cycle to control for diurnal effects on transcription. From the same plants, metabolites and enzyme activities were measured as well. Interestingly a gradual change could be observed over a wide range of temperatures. Some of which could be attributed to the CBF program. Keywords: time course, different temperatures
Project description:The goal of this project is to compare the primary metabolite profile in different tissue types of the model plant Arabidopsis thaliana. Specifically, plants were grown hydroponically under the long-day (16hr light/day) condition at 21C. Tissue samples, including leaves, inflorescences, and roots were harvest 4 1/2 weeks post sowing. Untargeted primary metabolites profiling was carried out using GCTOF.