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PROVIDER: PRJNA1138420 | ENA |
REPOSITORIES: ENA
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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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2024-09-02 | BIOMD0000000547 | BioModels
Project description:Arsenic (As) is highly toxic element to all forms of life and is a major environmental contaminant. Understanding acquisition, detoxification, and adaptation mechanisms in bacteria that are associated with host in arsenic-rich conditions can provide novel insights into dynamics of host-microbe-microenvironment interactions. In the present study, we have investigated an arsenic resistance mechanism acquired during the evolution of a particular lineage in the population of Xanthomonas oryzae pv. oryzae (Xoo), which is a serious plant pathogen infecting rice. Our study revealed the horizontal acquisition of a novel chromosomal 12kb ars cassette in Xoo IXO1088 that confers high resistance to arsenate/arsenite. The ars cassette comprises several genes that constitute an operon induced in the presence of arsenate/arsenite. This cassette has spread in lineage with highly virulent strains owing to a particular lineage’s evolutionary success. Further, we performed the transcriptomic analysis of Xoo strain IXO1088 under arsenate/arsenite exposure using RNA sequencing. The transcriptomic analysis revealed that arsenic detoxification and efflux, oxidative stress response, iron acquisition/storage, and damage repair are the main cellular responses to arsenic exposure. The study provides useful insights into the acquisition, detoxification, and adaptation mechanisms among Xoo populations to adapt under arsenic-rich environmental conditions.
2021-05-17 | GSE163417 | GEO
Project description:Arsenic exposure is a global health problem. Millions of people encounter arsenic through contaminated drinking water, consumption, and inhalation. The arsenic response locus in budding yeast is responsible for the detoxification of arsenic and its removal from the cell. This locus constitutes a conserved pathway ranging from prokaryotes to higher eukaryotes. The goal of this study was to identify how the arsenic response locus is regulated in an arsenic dependent manner. An affinity enrichment strategy called CRISPR-Chromatin Affinity Purification with Mass Spectrometry (CRISPR-ChAP-MS) was used that provides for the proteomic characterization of a given locus. CRISPR-ChAP-MS was applied to the arsenic response locus and uncovered 40 nuclear-annotated proteins showing enrichment. Functional assays, identified the histone acetyltransferase activity of SAGA and the ATPase chromatin remodeling activity of SWI/SNF to be required for activation of the locus. Furthermore, SAGA and SWI/SNF were both found to specifically organize the chromatin structure at the arsenic response locus for activation of gene transcription. This study provides the first proteomic characterization of an arsenic response locus and key insight into the mechanism of transcriptional activation that is necessary for detoxification of arsenic from the cell.
2020-05-07 | PXD009902 | Pride
Project description:Chronic arsenic exposure can lead to various health issues including cancer. There has been a growing concern about co-exposure to various prevalent lifestyle habits and their role in the enhancement of arsenic toxicity. Smokeless tobacco (SLT) products are extensively consumed in many South Asian countries, where their use frequently co-occurs with exposure to arsenic from contaminated groundwater. To decipher the oral epithelial cell responses to arsenic and SLT alone and in co-exposure, we performed multi-omics analyses of DNA methylome, transcriptomic reprogramming and genotoxic effects in controlled experimental settings. Chronic exposure studies revealed hypomethylation of genes involved in inflammation response and apoptosis, further corroborated by the upregulation of genes involved in these processes due to arsenic and the combined treatment in acute exposure setting. Next, to validate the omics results at the phenotypic level, we observed a dose dependent decrease in cell viability, induction of DNA damage, cell cycle changes, and an increase in apoptotic cells, with the most pronounced effects observed under arsenic and SLT co-exposure conditions. The observed DNA damage was likely the result of apoptosis induction, as chronic exposure experiments based on whole-exome sequencing did not reveal increased mutagenicity following the arsenic and/or SLT exposure. Our integrative omics study provides insights into both chronic and acute responses to arsenic and SLT co-exposure, with both types of responses converging on some of the same mechanisms. We identified large-scale epigenomic and transcriptomic reprograming associated with arsenic and SLT co-exposure, alongside genotoxic effects presumably manifesting as consequences of apoptosis induction. The findings point to a role of arsenic and SLT in altering key molecular responses, especially in the context of the co-exposure, and call for further studies in humans in the areas of exposure, to validate the observed mechanisms.
2024-12-04 | GSE269688 | GEO
Project description:Chronic arsenic exposure can lead to various health issues including cancer. There has been a growing concern about co-exposure to various prevalent lifestyle habits and their role in the enhancement of arsenic toxicity. Smokeless tobacco (SLT) products are extensively consumed in many South Asian countries, where their use frequently co-occurs with exposure to arsenic from contaminated groundwater. To decipher the oral epithelial cell responses to arsenic and SLT alone and in co-exposure, we performed multi-omics analyses of DNA methylome, transcriptomic reprogramming and genotoxic effects in controlled experimental settings. Chronic exposure studies revealed hypomethylation of genes involved in inflammation response and apoptosis, further corroborated by the upregulation of genes involved in these processes due to arsenic and the combined treatment in acute exposure setting. Next, to validate the omics results at the phenotypic level, we observed a dose dependent decrease in cell viability, induction of DNA damage, cell cycle changes, and an increase in apoptotic cells, with the most pronounced effects observed under arsenic and SLT co-exposure conditions. The observed DNA damage was likely the result of apoptosis induction, as chronic exposure experiments based on whole-exome sequencing did not reveal increased mutagenicity following the arsenic and/or SLT exposure. Our integrative omics study provides insights into both chronic and acute responses to arsenic and SLT co-exposure, with both types of responses converging on some of the same mechanisms. We identified large-scale epigenomic and transcriptomic reprograming associated with arsenic and SLT co-exposure, alongside genotoxic effects presumably manifesting as consequences of apoptosis induction. The findings point to a role of arsenic and SLT in altering key molecular responses, especially in the context of the co-exposure, and call for further studies in humans in the areas of exposure, to validate the observed mechanisms.
2024-12-04 | GSE269103 | GEO
Project description:Chronic exposure to arsenic is associated with dermatological and non-dermatological disorders. Consumption of arsenic contaminated drinking water results in accumulation of arsenic in liver, spleen, kidneys, lungs and gastrointestinal tract. Although, arsenic is cleared from these sites, a substantial amount of residual arsenic is left in keratin-rich tissues such as skin. Epidemiological studies on arsenic suggest the association of skin cancer upon arsenic exposure, however, the exact mechanism of arsenic induced carcinogenesis is not completely understood. We have developed a cell line-based model to understand the molecular mechanisms involved in arsenic mediated toxicity and carcinogenicity. Human skin keratinocyte cell line, HaCaT was exposed to 100nM sodium arsenite for six months. We observed an increase in the basal ROS levels in arsenic exposed cells along with the increase in anti-apoptotic proteins. SILAC-based quantitative proteomics approach resulted in the identification and quantitation of 2,181 proteins of which 39 proteins were found to be overexpressed (≥2-fold) and 56 downregulated (≤2-fold) upon chronic arsenic exposure. Our study provides comprehensive insights into the molecular basis of chronic arsenic exposure on skin.
2017-01-02 | PXD001645 | Pride
Project description:Arsenic poses a global threat to living organisms, compromising crop security and yield. Limited understanding of the transcriptional network integrating arsenic tolerance mechanisms with plant developmental responses hinders the development of strategies against this menace. Here, we employed an integrative genomic approach in Arabidopsis thaliana, involving a high-throughput yeast one-hybrid assay, and a transcriptomic analysis coupled with a transcription factor binding site enrichment analysis in gene expression clusters, to uncover novel transcriptional regulators of the arsenic response. We identified the GLABRA2 (GL2) transcription factor as a novel regulator of arsenic tolerance, revealing a wider regulatory role beyond its established function as a repressor of root hair formation. Furthermore, we found that ANTHOCYANINLESS2 (ANL2), a GL2 subfamily member, acts redundantly with this transcription factor in the regulation of arsenic signaling. Both transcription factors act as repressors of arsenic response. gl2 and anl2 mutants exhibit enhanced tolerance and reduced arsenic accumulation. Transcriptional analysis in the gl2 mutant unveils potential regulators of arsenic tolerance. These findings highlight GL2 and ANL2 as novel integrators of the arsenic response with developmental outcomes, offering insights for developing safer crops with reduced arsenic content and increased tolerance to this hazardous metalloid.
2024-08-31 | GSE255066 | GEO
Project description:Arsenic poses a global threat to living organisms, compromising crop security and yield. Limited understanding of the transcriptional network integrating arsenic tolerance mechanisms with plant developmental responses hinders the development of strategies against this menace. Here, we employed an integrative genomic approach in Arabidopsis thaliana, involving a high-throughput yeast one-hybrid assay, and a transcriptomic analysis coupled with a transcription factor binding site enrichment analysis in gene expression clusters, to uncover novel transcriptional regulators of the arsenic response. We identified the GLABRA2 (GL2) transcription factor as a novel regulator of arsenic tolerance, revealing a wider regulatory role beyond its established function as a repressor of root hair formation. Furthermore, we found that ANTHOCYANINLESS2 (ANL2), a GL2 subfamily member, acts redundantly with this transcription factor in the regulation of arsenic signaling. Both transcription factors act as repressors of arsenic response. gl2 and anl2 mutants exhibit enhanced tolerance and reduced arsenic accumulation. Transcriptional analysis in the gl2 mutant unveils potential regulators of arsenic tolerance. These findings highlight GL2 and ANL2 as novel integrators of the arsenic response with developmental outcomes, offering insights for developing safer crops with reduced arsenic content and increased tolerance to this hazardous metalloid.
2024-08-31 | GSE255065 | GEO
Project description:Our main objectives wereto investigate the molecular mechanisms involved in metal toxicity and detoxification in the field using juvenile yellow perch subjected to differents levels of this metal exposure. Recent local adaptation to pollution has been evidenced in several organisms inhabiting environments heavily contaminated by metals. Nevertheless, the molecular mechanisms underlying adaptation to high metal concentrations are poorly understood, especially in fishes. Yellow perch (Perca flavescens) populations from lakes in the mining area of Rouyn-Noranda (QC, Canada) have been faced with metal contamination for about 90 years. Here, we examine gene transcription patterns of fish reciprocally transplanted between a reference and a metal-contaminated lake and also fish caged in their native lake. After four weeks, 111 genes were differentially transcribed in metal-naïve fish transferred to the metal-contaminated lake, revealing a plastic response to metal exposure. Genes involved in the citric cycle and beta-oxidation pathways were under-transcribed, suggesting a potential strategy to mitigate the effects of metal stress by reducing energy turnover. However, metal-contaminated fish transplanted to the reference lake did not show any transcriptomic response, indicating a reduced plastic response capability to sudden reduction in metal concentrations. Moreover, the transcription of other genes, especially ones involved in energy metabolism, was affected by caging. Overall, our results highlight environmental stress response mechanisms in yellow perch at the transcriptomic level and support a rapid adaptive response to metal exposure through genetic assimilation. Comparison between fish Op and OpâOp using a pairwise design corresponding to the cage experiment in the reference lake Opasatica (Op), comparison between fish Du and DuâDu using a pairwise design corresponding to the cage experiment in the metal contaminated lake Dufault (Du), comparison between fish from reference lake transplanted to the metal contaminated lake (OpâDu) and fish from reference lake caged in their own lake (OpâOp) using pairwise design corresponding to the experiment of metal contamination, comparison between fish from metal contaminated lake transplanted to the reference lake (DuâOp) and fish from the metal contaminated lake caged in their own lake (DuâDu) using pairwise design corresponding to the depuration experiment.
2016-01-11 | E-GEOD-76723 | biostudies-arrayexpress