THE GOOD, THE BAD, AND THE TOXIC: DECIPHERING HORMESIS IN DAPHNIA MAGNA EXPOSED TO AN ENERGETIC COMPOUND
Ontology highlight
ABSTRACT:
ORGANISM(S): Daphnia magna
PROVIDER: GSE43960 | GEO | 2013/02/01
SECONDARY ACCESSION(S): PRJNA188234
REPOSITORIES: GEO
Similar Datasets
Project description:Hormesis is a dose response phenomenon characterized by a stimulation of an organismal response at low doses of a chemical and inhibition of the response (toxicity) at a higher dose. In the present study, Daphnia magna were exposed to the energetic compound 2,4,6-trinitrotoluene (TNT) for 21 days, and the endpoints survival, growth (length and dry weight), and reproduction (number of neonates per survivor) were assesed, identifying hormetic responses at the lower treatment levels. In order to elucidate the mechanisms leading to hormesis, microarray analysis was performed at 0.004 (hormetic), 0.12 (sometimes hormetic), and 1.85 (toxic) mg/L TNT. Functional and transcriptional benchmark dose analyses performed on differentially expressed genes suggested the involvement of lipid metabolism in hormetic responses and subsequently lipidomic analysis was performed on the same treatments. Lipid analysis supported the hypothesis that TNT exposure affected lipid metabolism, and showed that hormetic effects could be related to increases in some polyunsaturated fatty acids and ecosanoids known to be involved in Daphnia growth and reproduction. Chronic toxicity tests was designed to identify the hormetic range of D. magna responses to TNT. Daphnia magna younger than 24 h old and obtained from in-house cultures at the U.S. Army Engineer Research and Development Center, Environmental Laboratory (Vicksburg, MS) were used to initiate the bioassay. The experimental design consisted of one D. magna per test chamber and 10 test chambers per treatment level. In the microarray mass exposure, nominal treatment levels were 0.004, 0.02, 0.12, 0.44, and 1.85 mg/L. Based on the results of the testing in the 50 ml beakers, organisms from three treatments were selected for analysis of gene expression: 0.004, 0.12, and 1.85 mg/L. These treatments were selected to represent a hormetic concentration (0.004 mg/L), a toxic concentration (1.85 mg/L), and an intermediate concentration (0.12 mg/L). A total of 23 arrays used, with 5-6 replicates per each dose (solvent control, 0.004 mg/L, 0.12 mg/L, and 1.85 mg/L).
2013-02-01 | E-GEOD-43960 | biostudies-arrayexpress
Project description:We tested the hypothesis that the behavioral response to selenium (Se) follows a hormetic dose response pattern, manifested through the functions of selenoproteins within the brain. We measured anxiety-related behaviors in zebrafish (Danio rerio) at deficient, control and supplemented levels of dietary Se, and measured the transcriptional response of selenoprotein genes important for neuroprotection. We also used a microarray approach to assess the transcriptomic response of the midbrain to Se. The behavioral response to Se was characterized by hormesis, and the direction, magnitude, and shape of the hormetic responses were dependent on both sex and zebrafish population. Transcription of selenoproteins within the midbrain also responded to Se in a similar hormetic dose-dependent manner, with sex and population influencing the trajectory of the responses. The hormetic behavioral response to Se may therefore be manifested through selenoproteins in the brain, but the influence is not direct.
2014-05-01 | GSE52484 | GEO
Project description:We tested the hypothesis that the behavioral response to selenium (Se) follows a hormetic dose response pattern, manifested through the functions of selenoproteins within the brain. We measured anxiety-related behaviors in zebrafish (Danio rerio) at deficient, control and supplemented levels of dietary Se, and measured the transcriptional response of selenoprotein genes important for neuroprotection. We also used a microarray approach to assess the transcriptomic response of the midbrain to Se. The behavioral response to Se was characterized by hormesis, and the direction, magnitude, and shape of the hormetic responses were dependent on both sex and zebrafish population. Transcription of selenoproteins within the midbrain also responded to Se in a similar hormetic dose-dependent manner, with sex and population influencing the trajectory of the responses. The hormetic behavioral response to Se may therefore be manifested through selenoproteins in the brain, but the influence is not direct. We performed a microarray analysis comparing the midbrain-specific transcriptome between male zebrafish from two populations (Pargana: P and Transgenic Mosaic 1: T) fed either a control, Se deficient, or Se supplemented diet (17 total samples: 9 fish per population, 3 fish per diet: missing 1 P control sample).
2014-05-01 | E-GEOD-52484 | biostudies-arrayexpress
Project description:Hormesis occurs when a low level stress elicits adaptive beneficial responses that protect against subsequent exposure to severe stress. Recent findings suggest that mild oxidative and thermal stress can extend lifespan by hormetic mechanisms. Here we show that the botanical pesticide plumbagin, while toxic to C. elegans nematodes at high doses, extends lifespan at low doses. Because plumbagin is a naphthoquinone that generates free radicals in vivo, we investigated whether it extends lifespan by activating an adaptive cellular stress response pathway. Mammalian NF-E2-related factor 2 (Nrf2) and its C. elegans ortholog SKN-1, mediate protective responses to oxidative stress by promoting target gene expression via antioxidant response elements (ARE). Genetic analyses showed that skn-1 mediates plumbagin’s lifespan-extending effect in C. elegans. Further screening of a series of plumbagin analogs identified three additional naphthoquinones that could induce SKN-1 targets in C. elegans. Naphthazarin showed skn-1-dependent lifespan extension, over an extended dose range compared to plumbagin, while the other naphthoquinones, oxoline and menadione, had differing effects on C. elegans survival and failed to activate ARE reporter expression in cultured mammalian cells. Our findings reveal the potential for low doses of naturally occurring naphthoquinones to extend lifespan by engaging a specific adaptive cellular stress response pathway.
2012-03-21 | GSE28301 | GEO
Project description:To understand molecular mechanisms of the chronic, sublethal toxicity of 2,4,6-trinitrotoluene (TNT), a widely used ordnance compound of public concerns, we constructed a microarray consisting of 4,032 cDNA isolated from the earthworm Eisenia fetida using the suppressive subtractive hybridization technique. Worms were exposed to a gradient of TNT-spiked soil for 28 days. Based on the reproduction response to TNT, four treatments, i.e., control, 7, 35 and 139 ppm, were selected for gene expression studies. Keywords: Sublethal toxicity of TNT (dose-response) to earthworm (Eisenia fetida)
2007-10-15 | GSE7024 | GEO
Project description:The health and resilience of species in natural environments are increasingly challenged by complex anthropogenic stressor combinations including climate change, habitat encroachment, and chemical contamination. To better understand impacts of these stressors, we examined the individual- and combined-stressor impacts of malaria infection, food limitation, and 2,4,6-trinitrotoluene (TNT) exposures on gene expression in livers of Western fence lizard (WFL, Sceloporus occidentalis) using custom WFL transcriptome-based microarrays. Computational analysis including annotation enrichment and correlation analysis identified putative functional mechanisms between transcript expression and toxicological phenotype. TNT exposure increased transcript expression for genes involved in erythropoiesis, potentially in response to TNT-induced anemia and/or methemoglobinemia, and caused dose-specific effects on genes involved in lipid and overall energy metabolism consistent with a hormesis response of growth stimulation at low doses contrasted with adverse effects on lizard growth at high doses. Functional enrichment and inguinal fat body weights suggest inhibition of lipid mobilization and catabolism by TNT coupled with a decreased overall energy budget. Malaria infection elicited enrichment of the expression of multiple immune-related functions likely corresponding to increased white blood cell (WBC) counts. Food limitation alone enriched functions related to cellular energy production and decreased expression of immune response consistent with a decrease in WBC levels. Despite these findings, the lizards demonstrated immune resilience to malaria infection under food limitation with transcriptional results indicating a fully competent immune response to malaria, even under bioenergetic constraints. Interestingly, each TNT and malaria individually tended to increase transcriptional expression of immune-related genes and increase overall WBC concentrations in blood; responses that were retained in the TNT x malaria combined exposure. The results demonstrate complex and sometimes unexpected responses to multiple stressors where the lizards displayed remarkable resiliency to the stressor combinations investigated.
2018-11-15 | GSE116021 | GEO
Project description:The health and resilience of species in natural environments are increasingly challenged by complex anthropogenic stressor combinations including climate change, habitat encroachment, and chemical contamination. To better understand impacts of these stressors, we examined the individual- and combined-stressor impacts of malaria infection, food limitation, and 2,4,6-trinitrotoluene (TNT) exposures on gene expression in livers of Western fence lizard (WFL, Sceloporus occidentalis) using custom WFL transcriptome-based microarrays. Computational analysis including annotation enrichment and correlation analysis identified putative functional mechanisms between transcript expression and toxicological phenotype. TNT exposure increased transcript expression for genes involved in erythropoiesis, potentially in response to TNT-induced anemia and/or methemoglobinemia, and caused dose-specific effects on genes involved in lipid and overall energy metabolism consistent with a hormesis response of growth stimulation at low doses contrasted with adverse effects on lizard growth at high doses. Functional enrichment and inguinal fat body weights suggest inhibition of lipid mobilization and catabolism by TNT coupled with a decreased overall energy budget. Malaria infection elicited enrichment of the expression of multiple immune-related functions likely corresponding to increased white blood cell (WBC) counts. Food limitation alone enriched functions related to cellular energy production and decreased expression of immune response consistent with a decrease in WBC levels. Despite these findings, the lizards demonstrated immune resilience to malaria infection under food limitation with transcriptional results indicating a fully competent immune response to malaria, even under bioenergetic constraints. Interestingly, each TNT and malaria individually tended to increase transcriptional expression of immune-related genes and increase overall WBC concentrations in blood; responses that were retained in the TNT x malaria combined exposure. The results demonstrate complex and sometimes unexpected responses to multiple stressors where the lizards displayed remarkable resiliency to the stressor combinations investigated.
2018-11-15 | GSE116025 | GEO
Project description:The health and resilience of species in natural environments are increasingly challenged by complex anthropogenic stressor combinations including climate change, habitat encroachment, and chemical contamination. To better understand impacts of these stressors, we examined the individual- and combined-stressor impacts of malaria infection, food limitation, and 2,4,6-trinitrotoluene (TNT) exposures on gene expression in livers of Western fence lizard (WFL, Sceloporus occidentalis) using custom WFL transcriptome-based microarrays. Computational analysis including annotation enrichment and correlation analysis identified putative functional mechanisms between transcript expression and toxicological phenotype. TNT exposure increased transcript expression for genes involved in erythropoiesis, potentially in response to TNT-induced anemia and/or methemoglobinemia, and caused dose-specific effects on genes involved in lipid and overall energy metabolism consistent with a hormesis response of growth stimulation at low doses contrasted with adverse effects on lizard growth at high doses. Functional enrichment and inguinal fat body weights suggest inhibition of lipid mobilization and catabolism by TNT coupled with a decreased overall energy budget. Malaria infection elicited enrichment of the expression of multiple immune-related functions likely corresponding to increased white blood cell (WBC) counts. Food limitation alone enriched functions related to cellular energy production and decreased expression of immune response consistent with a decrease in WBC levels. Despite these findings, the lizards demonstrated immune resilience to malaria infection under food limitation with transcriptional results indicating a fully competent immune response to malaria, even under bioenergetic constraints. Interestingly, each TNT and malaria individually tended to increase transcriptional expression of immune-related genes and increase overall WBC concentrations in blood; responses that were retained in the TNT x malaria combined exposure. The results demonstrate complex and sometimes unexpected responses to multiple stressors where the lizards displayed remarkable resiliency to the stressor combinations investigated.
2018-11-15 | GSE116024 | GEO
Project description:Gut and rest of body tissue from fifth instar larvae which fed for three days a diet containing different doses of gossypol. Transcriptional profiling comparing gut and rest of body samples for three gossypol concentrations (0%, 0.016%-hormetic dose & 0.16%-detrimental dose). Hormesis is a biphasic biological response characterized by the stimulatory effect at relatively low amounts of chemical compounds otherwise known to be detrimental at higher concentrations. A hormetic response in larval growth rates has been observed in cotton-feeding insects in response to increasing concentrations of gossypol, a toxic metabolite found in the pigment glands of some Malvaceae plants. We investigated the developmental effect of gossypol in the cotton bollworm, Helicoverpa armigera, an important heliothine pest species, by exposing larvae to different doses of this metabolite in their diet. In addition, we sought to determine the underlying transcriptional responses to different gossypol doses. Larval weight gain, pupal weight and larval development time were measured in feeding experiments and a hormetic response was seen for the first two characters. On the basis of net larval weight gain responses to gossypol, three treatments, that is 0%, 0.016% and 0.16% gossypol , were selected for transcript profiling in the gut and the rest of the body in a two-color double reference design microarray experiment.
2011-10-20 | GSE33080 | GEO
Project description:Gut and rest of body tissue from fifth instar larvae which fed for three days a diet containing different doses of gossypol. Transcriptional profiling comparing gut and rest of body samples for three gossypol concentrations (0%, 0.016%-hormetic dose & 0.16%-detrimental dose). Hormesis is a biphasic biological response characterized by the stimulatory effect at relatively low amounts of chemical compounds otherwise known to be detrimental at higher concentrations. A hormetic response in larval growth rates has been observed in cotton-feeding insects in response to increasing concentrations of gossypol, a toxic metabolite found in the pigment glands of some Malvaceae plants. We investigated the developmental effect of gossypol in the cotton bollworm, Helicoverpa armigera, an important heliothine pest species, by exposing larvae to different doses of this metabolite in their diet. In addition, we sought to determine the underlying transcriptional responses to different gossypol doses. Larval weight gain, pupal weight and larval development time were measured in feeding experiments and a hormetic response was seen for the first two characters. On the basis of net larval weight gain responses to gossypol, three treatments, that is 0%, 0.016% and 0.16% gossypol , were selected for transcript profiling in the gut and the rest of the body in a two-color double reference design microarray experiment. Two-color double reference design. Reference sample was the 0% (CT) gossypol condition (either Gut or Rest of Body) or one of two experimental conditions {0.016(T5) and 0.16%(T7)}. Biological replicates: 4 (10 individuals per replicate). 32 samples total.
2011-10-19 | E-GEOD-33080 | biostudies-arrayexpress