Transcriptome profile analysis reveals putative molecular mechanisms of 5-aminolevulinic acid toxicity
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PROVIDER: PRJNA840868 | ENA |
REPOSITORIES: ENA
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2023-05-15 | GSE203437 | GEO
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2012-06-29 | E-GEOD-30216 | biostudies-arrayexpress
Project description:Gene expression profiling in soybean under aluminum stress: mechanisms of magnesium amelioration of aluminum toxicity at gene expression level. Micro-molar concentrations of magnesium in culture solution has been shown to ameliorate Al toxicity in soybean and other leguminous species. Different theories have been proposed to explain the chemical mechanisms of how the two ions interact to neutralize the toxic effect of aluminum in the plant root system. To understand the molecular mechanisms of the phenomenon at the gene expression level in soybean, we undertook a comparative transcriptome analysis in Al-tolerant and Al-sensitive genotypes treated with aluminum alone or aluminum plus magnesium using DNA microarrays. The results revealed magnesium enhances Al-tolerance level in the Al-tolerant genotype by down-regulating genes commonly induced in response to Al toxicity. We hypothesized that the magnesium-mediated alleviation of Al toxicity in the Al-tolerant genotype emanates from reduction in energy expenditure of gene expression induced in response to Al stress. Conversely, magnesium appears to ameliorate Al toxicity in the sensitive genotype by dual mechanisms of increasing the expression level of several genes involved in Al-tolerance and decreasing the expression level of most genes. Keywords: Soybean, aluminum toxicity, magnesium, transcriptome Two genotypes: PI 416937 (p) and Young (y); two treatments: Aluminum (Al) or Al+magnesium (Mg); two time points: 12 and 72 hrs; 3 replicates.
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Project description:A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatic analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top-ranking biological functions perturbed by silica exposure in the A549 cells and rat lungs. The involvement of oxidative stress and apoptosis in the silica-induced pulmonary toxicity was confirmed by ELISA and confocal microscopy analysis, respectively, of the silica-exposed A549 cells. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study, may result in a better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure. 20 samples were analyzed in this experiment. RNA from rat lung samples was isolated for gene expression studies. Rats were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days) or air. Lung gene expression profiling was performed using rat lung samples, 8 for silica exposed and 12 for air-exposed controls at 0 weeks post-exposure time period.
2012-06-29 | E-GEOD-30178 | biostudies-arrayexpress
Project description:Zinc (Zn) is known to be relatively toxic to some soil-living invertebrates including the ecologically important enchytraeid worms. To reveal the molecular mechanisms of zinc toxicity we assessed the gene expression profile of Enchytraeus crypticus (Enchytraeidae), exposed to the reproduction effect concentrations EC10 and EC50, over 4 consecutive days, using a high-throughput microarray (species customized). Three main mechanisms of toxicity to Zn were observed: 1) Zn trafficking (upregulation of zinc transporters, a defence response to regulate the cellular zinc level), 2) oxidative stress (variety of defence mechanisms, triggered by Reactive Oxygen Species (ROS) generated by Zn), and 3) effects on the nervous system (possibly the primary lesion explaining the avoidance behaviour and also why enchytraeids are relatively susceptible to Zn). The adverse outcome at the organism level (reproduction EC50) could be predicted based on gene expression (male gonad development, oocyte maturation), with Zn at the EC50 affecting processes related to higher stress levels. The gene expression response was time-specific and reflected the cascade of events taking place over-time. The 1 to 4 days of exposure design was a good strategy to capture the sequence of events towards zinc adverse outcomes in E. crypticus.
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Project description:Glyphosate (GLY) is one of the most applied agrochemicals in the world, and its exposure has aroused the public health concern. Freshwater planarian is an ideal test organism for examining toxicity of pollutants and has become an emerging animal model for toxicology studies. However, potential toxicity mechanism of GLY in planarian has not been comprehensively studied. To explore the toxicity effects and molecular mechanism involved in GLY exposure of planarian, we analyzed the acute toxicity, histological change, DNA damage and transcriptional responses of freshwater planarian Dugesia japonica subjected to GLY. Results indicated that morphological malformation, histopathological change and genome DNA damage were observed after GLY exposure for different time. Transcriptomic analysis showed that numerous differentially expressed genes (DEGs) were obtained at 1, 3 and 5 d after exposure. GO and KEGG enrichment analysis of these DEGs was carried out and a dynamic and global view was obtained in planarian after GLY exposure at the transcriptomic level. Furthermore, qRT-PCR was performed on nine DEGs associated with detoxification, apoptosis, stress response, DNA repair, etc. The expression patterns were well consistent with the RNA-seq results at different timepoints, which confirmed the accuracy and reliability of the transcriptome data. Collectively, our results established that GLY could pose adverse effects on the morphology, histoarchitecture as well as genome DNA of D. japonica, and the planarians are capable of responding to the disadvantageous GLY stress by dysregulating the related genes and their participated in pathways concerning immune response, detoxification, energy metabolism, DNA damage repair, etc. To the best of our knowledge, this is the first report of transcriptomic analysis of freshwater planarian exposed to environmental pollutant, and it provided detailed sequencing data deriving from transcriptome profiling to deepen our understanding of the molecular toxicity mechanism of GLY on planarians.
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Project description:Talemi2014 - Arsenic toxicity and
detoxification mechanisms in yeast
The model implements arsenite (AsIII)
transport regulation, its distribution within main cellular AsIII
pools and detoxification. The intracellular As pools considered are
free AsIII (AsIIIin), protein-bound AsIII (AsIIIprot), glutathione
conjugated AsIII (AsGS3) and vacuolar sequestered AsIII (vAsGS3).
This model is described in the article:
Mathematical modelling of
arsenic transport, distribution and detoxification processes in
yeast.
Talemi SR, Jacobson T, Garla V,
Navarrete C, Wagner A, Tamás MJ, Schaber J.
Mol. Microbiol. 2014 Jun; 92(6):
1343-1356
Abstract:
Arsenic has a dual role as causative and curative agent of
human disease. Therefore, there is considerable interest in
elucidating arsenic toxicity and detoxification mechanisms. By
an ensemble modelling approach, we identified a best
parsimonious mathematical model which recapitulates and
predicts intracellular arsenic dynamics for different
conditions and mutants, thereby providing novel insights into
arsenic toxicity and detoxification mechanisms in yeast, which
could partly be confirmed experimentally by dedicated
experiments. Specifically, our analyses suggest that: (i)
arsenic is mainly protein-bound during short-term (acute)
exposure, whereas glutathione-conjugated arsenic dominates
during long-term (chronic) exposure, (ii) arsenic is not stably
retained, but can leave the vacuole via an export mechanism,
and (iii) Fps1 is controlled by Hog1-dependent and
Hog1-independent mechanisms during arsenite stress. Our results
challenge glutathione depletion as a key mechanism for arsenic
toxicity and instead suggest that (iv) increased glutathione
biosynthesis protects the proteome against the damaging effects
of arsenic and that (v) widespread protein inactivation
contributes to the toxicity of this metalloid. Our work in
yeast may prove useful to elucidate similar mechanisms in
higher eukaryotes and have implications for the use of arsenic
in medical therapy.
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BIOMD0000000547.
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2024-09-02 | BIOMD0000000547 | BioModels
Project description:Gene expression profiling in soybean under aluminum stress: mechanisms of magnesium amelioration of aluminum toxicity at gene expression level. Micro-molar concentrations of magnesium in culture solution has been shown to ameliorate Al toxicity in soybean and other leguminous species. Different theories have been proposed to explain the chemical mechanisms of how the two ions interact to neutralize the toxic effect of aluminum in the plant root system. To understand the molecular mechanisms of the phenomenon at the gene expression level in soybean, we undertook a comparative transcriptome analysis in Al-tolerant and Al-sensitive genotypes treated with aluminum alone or aluminum plus magnesium using DNA microarrays. The results revealed magnesium enhances Al-tolerance level in the Al-tolerant genotype by down-regulating genes commonly induced in response to Al toxicity. We hypothesized that the magnesium-mediated alleviation of Al toxicity in the Al-tolerant genotype emanates from reduction in energy expenditure of gene expression induced in response to Al stress. Conversely, magnesium appears to ameliorate Al toxicity in the sensitive genotype by dual mechanisms of increasing the expression level of several genes involved in Al-tolerance and decreasing the expression level of most genes. Keywords: Soybean, aluminum toxicity, magnesium, transcriptome
2010-10-04 | GSE18518 | GEO