1.0 mM As(III) stressed wild-type vs (non-stressed) wild-type after 1 hour
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE6066 | GEO | 2007/10/18
SECONDARY ACCESSION(S): PRJNA104437
REPOSITORIES: GEO
Similar Datasets
Project description:volved enabling cells to evade toxicity and acquire tolerance. Herein, we explored how Saccharomyces cerevisiae (budding yeast) respond to trivalent arsenic (arsenite) by quantitative and kinetic transcriptome, proteome and sulfur metabolite profiling. Arsenite exposure affected transcription of genes encoding functions related to protein biosynthesis, arsenic detoxification, oxidative stress defense, redox maintenance and proteolytic activity. Importantly, enzymes involved in sulfate assimilation and glutathione biosynthesis were induced at both gene and protein levels. Kinetic metabolic profiling evidenced a significant increase in the pools of sulfur metabolites as well as elevated glutathione levels. Moreover, the flux in the sulfur assimilation pathway as well as the glutathione synthesis rate strongly increased with a concomitant reduction of sulfur incorporation into proteins. By combining comparative genomics and molecular analyses, we pin-pointed transcription factors that mediate thecore of the transcriptional response to arsenite. Taken together, our data reveals that arsenite-exposed cells channel a large part of assimilated sulfur into glutathione biosynthesis and we provide evidence that the transcriptional regulators Yap1p and Met4p control this response in concert. Keywords: stress
2007-10-18 | GSE6071 | GEO
Project description:Arsenic is ubiquitously present in nature and various mechanisms have evolved enabling cells to evade toxicity and acquire tolerance. Herein, we explored how Saccharomyces cerevisiae (budding yeast) respond to trivalent arsenic (arsenite) by quantitative and kinetic transcriptome, proteome and sulfur metabolite profiling. Arsenite exposure affected transcription of genes encoding functions related to protein biosynthesis, arsenic detoxification, oxidative stress defense, redox maintenance and proteolytic activity. Importantly, enzymes involved in sulfate assimilation and glutathione biosynthesis were induced at both gene and protein levels. Kinetic metabolic profiling evidenced a significant increase in the pools of sulfur metabolites as well as elevated glutathione levels. Moreover, the flux in the sulfur assimilation pathway as well as the glutathione synthesis rate strongly increased with a concomitant reduction of sulfur incorporation into proteins. By combining comparative genomics and molecular analyses, we pin-pointed transcription factors that mediate thecore of the transcriptional response to arsenite. Taken together, our data reveals that arsenite-exposed cells channel a large part of assimilated sulfur into glutathione biosynthesis and we provide evidence that the transcriptional regulators Yap1p and Met4p control this response in concert. Keywords: stress
2007-10-18 | GSE6067 | GEO
Project description:Arsenic is ubiquitously present in nature and various mechanisms have evolved enabling cells to evade toxicity and acquire tolerance. Herein, we explored how Saccharomyces cerevisiae (budding yeast) respond to trivalent arsenic (arsenite) by quantitative and kinetic transcriptome, proteome and sulfur metabolite profiling. Arsenite exposure affected transcription of genes encoding functions related to protein biosynthesis, arsenic detoxification, oxidative stress defense, redox maintenance and proteolytic activity. Importantly, enzymes involved in sulfate assimilation and glutathione biosynthesis were induced at both gene and protein levels. Kinetic metabolic profiling evidenced a significant increase in the pools of sulfur metabolites as well as elevated glutathione levels. Moreover, the flux in the sulfur assimilation pathway as well as the glutathione synthesis rate strongly increased with a concomitant reduction of sulfur incorporation into proteins. By combining comparative genomics and molecular analyses, we pin-pointed transcription factors that mediate thecore of the transcriptional response to arsenite. Taken together, our data reveals that arsenite-exposed cells channel a large part of assimilated sulfur into glutathione biosynthesis and we provide evidence that the transcriptional regulators Yap1p and Met4p control this response in concert. Keywords: stress
2007-10-18 | GSE6072 | GEO
Project description:Arsenic is ubiquitously present in nature and various mechanisms have evolved enabling cells to evade toxicity and acquire tolerance. Herein, we explored how Saccharomyces cerevisiae (budding yeast) respond to trivalent arsenic (arsenite) by quantitative and kinetic transcriptome, proteome and sulfur metabolite profiling. Arsenite exposure affected transcription of genes encoding functions related to protein biosynthesis, arsenic detoxification, oxidative stress defense, redox maintenance and proteolytic activity. Importantly, enzymes involved in sulfate assimilation and glutathione biosynthesis were induced at both gene and protein levels. Kinetic metabolic profiling evidenced a significant increase in the pools of sulfur metabolites as well as elevated glutathione levels. Moreover, the flux in the sulfur assimilation pathway as well as the glutathione synthesis rate strongly increased with a concomitant reduction of sulfur incorporation into proteins. By combining comparative genomics and molecular analyses, we pin-pointed transcription factors that mediate thecore of the transcriptional response to arsenite. Taken together, our data reveals that arsenite-exposed cells channel a large part of assimilated sulfur into glutathione biosynthesis and we provide evidence that the transcriptional regulators Yap1p and Met4p control this response in concert. Keywords: stress
2007-10-18 | GSE6070 | GEO
Project description:Arsenic is ubiquitously present in nature and various mechanisms have evolved enabling cells to evade toxicity and acquire tolerance. Herein, we explored how Saccharomyces cerevisiae (budding yeast) respond to trivalent arsenic (arsenite) by quantitative and kinetic transcriptome, proteome and sulfur metabolite profiling. Arsenite exposure affected transcription of genes encoding functions related to protein biosynthesis, arsenic detoxification, oxidative stress defense, redox maintenance and proteolytic activity. Importantly, enzymes involved in sulfate assimilation and glutathione biosynthesis were induced at both gene and protein levels. Kinetic metabolic profiling evidenced a significant increase in the pools of sulfur metabolites as well as elevated glutathione levels. Moreover, the flux in the sulfur assimilation pathway as well as the glutathione synthesis rate strongly increased with a concomitant reduction of sulfur incorporation into proteins. By combining comparative genomics and molecular analyses, we pin-pointed transcription factors that mediate thecore of the transcriptional response to arsenite. Taken together, our data reveals that arsenite-exposed cells channel a large part of assimilated sulfur into glutathione biosynthesis and we provide evidence that the transcriptional regulators Yap1p and Met4p control this response in concert. Keywords: stress, time course
2007-10-18 | GSE6068 | GEO
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.
This model is hosted on
BioModels Database
and identified by:
BIOMD0000000547.
To cite BioModels Database, please use:
BioModels Database:
An enhanced, curated and annotated resource for published
quantitative kinetic models.
To the extent possible under law, all copyright and related or
neighbouring rights to this encoded model have been dedicated to
the public domain worldwide. Please refer to
CC0
Public Domain Dedication for more information.
2014-09-04 | BIOMD0000000547 | BioModels
Project description:Arsenic is a human toxin and carcinogen commonly found as a contaminant in drinking water. Arsenite (AsIII) is the most toxic inorganic form, but recent evidence indicates that the metabolite monomethylarsonous acid (MMAIII) is even more toxic. We have used a chemical genomics approach to identify the genes that modulate the cellular toxicity of MMAIII and AsIII in the yeast Saccharomyces cerevisiae. Functional profiles provided evidence of the requirement of highly-conserved biological processes in the response against both arsenicals including tubulin folding, DNA double-strand break repair and chromatin modification. At the equitoxic doses of 150 µM MMAIII and 300 µM AsIII, genes related to glutathione were essential only for resistance to the former, suggesting a higher potency of MMAIII to disrupt glutathione metabolism than AsIII. Treatments with MMAIII induced an increase in glutathione levels, which correlated to the requirement of genes from the sulfur and methionine metabolic pathways. Many of the identified yeast genes have orthologs in humans that could potentially modulate arsenic toxicity in a similar manner as their yeast counterparts.
2009-09-03 | GSE17950 | GEO
Project description:This study was aimed at elucidating the significance of photorespiratory serine (Ser) production for cysteine (Cys) biosynthesis. For this purpose, sulfur (S) metabolism and its crosstalk with nitrogen (N) and carbon (C) metabolism were analyzed in wildtype Arabidopsis and its photorespiratory bou-2 mutant with impaired glycine decarboxylase (GDC) activity. Foliar glycine and Ser contents were enhanced in the mutant at day and night. The high Ser levels in the mutant cannot be explained by transcript abundances of genes of the photorespiratory pathway or two alternative pathways of Ser biosynthesis. Despite enhanced foliar Ser, reduced GDC activity mediated a decline in sulfur flux into major sulfur pools in the mutant, as a result of deregulation of genes of sulfur reduction and assimilation. Still, foliar Cys and glutathione contents in the mutant were enhanced. The use of Cys for methionine and glucosinolates synthesis was reduced in the mutant. Reduced GDC activity in the mutant downregulated Calvin Cycle and nitrogen assimilation genes, upregulated key enzymes of glycolysis and the tricarboxylic acid (TCA) pathway and modified accumulation of sugars and TCA intermediates. Thus, photorespiratory Ser production can be replaced by other metabolic Ser sources, but this replacement deregulates the cross-talk between S, N, and C metabolism.
2018-11-27 | GSE86380 | GEO
Project description:Arsenic (As) contamination of rice grains affects millions of people worldwide. In this study, we found that sulfur application (20As+120S) decreased As concentration in rice grains by 44 % compared to grains without sulfur application (20As+0S). Importantly, sulfur application decreased arsenate [As(V)] and arsenite [As(III)] concentration in rice grains significantly, while there was no significant effect on dimethylarsenate (DMA) concentration. To elucidate the molecular basis of As accumulation in rice grains, we performed Illumina sequencing to acquire the differentially expressed genes induced by arsenate and sulfur treatments. By contrast with the control, the expression of 1,000 genes was found to be changed significantly, with 46 genes up-regulated and 954 genes down-regulated in grains grown in arsenate-contaminated soil (20As+0S). Between samples of control and arsenate together with sulfur treatment (20As+120S), 1,169 genes expressed significantly differently, with 16 genes up-regulated and 1,153 genes down-regulated. Sulfur application significantly changed the expression of genes involved in As metabolism in rice grains, significantly down-regulated phosphate transporter gene OsPT23 and aquaporin gene OsTIP4;2, while ABC transporter genes (OsABCG5, OsABCI7_2 and OsABC6) and phytochelatin synthase genes (OsPCS1, OsPCS3 and OsPCS13) were up-regulated. These results provide an insight into the molecular basis of how sulfur assimilation regulates As accumulation in rice grains.
2015-07-01 | GSE48799 | GEO
Project description:Arsenic (As) exposure is a significant worldwide environmental health concern. Low dose, chronic arsenic exposure has been associated with higher risk of skin, lung, and bladder cancer, as well as cardiovascular disease and diabetes. While arsenic-induced biological changes play a role in disease pathology, little is known about the dynamic cellular changes due to arsenic exposure and withdrawal. In these studies, we seek to understand the molecular mechanisms behind the biological changes induced by chronic low doses of arsenic exposure. We used a comprehensive approach involving chromatin structural studies and mRNA microarray analyses to determine how chromatin structure and gene expression patterns change in response to chronic low dose arsenic exposure and its subsequent withdrawal. Our results show that cells exposed to low doses of sodium arsenite have distinct temporal and coordinated chromatin, gene expression and miRNA changes that are consistent with differentiation and activation of multiple biochemical pathways. Most of these temporal patterns in gene expression are reversed when arsenic was withdrawn. However, some of the gene expression patterns remained altered, plausibly as a result of an adaptive response by these cells. Additionally, these gene expression patterns correlated with changes in chromatin structure, further solidifying the role of chromatin structure in gene regulatory changes due to arsenite exposure. Lastly, we show that arsenite exposure influences gene regulation both at the transcription initiation as well as at the splicing level. Thus our results suggest that general patterns of alternative splicing, as well as expression of particular gene regulators, can be indicative of arsenite-induced cell transformation. A total of eight (8) samples with two biological replicates under four separate conditions: wild-type treated with deionized H2O for 36 days (NT); chronic low-dose arsenic exposure of 1 uM of sodium arsenite (iAs-T) for 36 days; chronic arsenic exposure of 1 uM of sodium arsenite for 26 days followed by removal of sodium arsenite for 10 days, measured at day 36 (iAs-Rev); and chronic arsenic exposure of 1 uM of sodium arsenite for 26 days, followed by removal of sodium arsenite exposure for 10 days, followed by 1 uM of chronic sodium arsenite exposure for 10 days (measured at day 46) (iAs-Rev-T).
2015-05-05 | E-GEOD-60760 | biostudies-arrayexpress