Trivalent arsenic inhibits the functions of chaperonin complex
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE5973 | GEO | 2010/07/26
SECONDARY ACCESSION(S): PRJNA97447
REPOSITORIES: GEO
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Project description:The goal of this study was to identify yeast mutants with arsenite hypersensitivity. Keywords: dose response Matched pools of yeast knockout (YKO) mutants were grown in paired growth media lacking or containing arsenite at various concentrations. The relative abundances of the YKO mutants were profiled using microarrays. Three types of pools were used in this study: (1) heterozygous diploid mutants; (2) haploid mutants obtained as progeny from the heterozygous diploid pool; and (3) haploid mutants also containing a null mutation of the prefoldin gene PFD1.
2010-07-26 | E-GEOD-5973 | biostudies-arrayexpress
Project description:The exact molecular mechanisms by which the environmental pollutant arsenic works in biological systems are not completely understood. Using an unbiased chemogenomics approach in Saccharomyces cerevisiae, we found that mutants of the chaperonin complex TRiC and the functionally related prefoldin complex are all hypersensitive to arsenic compared to a wild-type strain. In contrast, mutants with impaired ribosome functions were highly arsenic resistant. These observations led us to hypothesize that arsenic might inhibit TRiC function, required for folding of actin, tubulin, and other proteins postsynthesis. Consistent with this hypothesis, we found that arsenic treatment distorted morphology of both actin and microtubule filaments. Moreover, arsenic impaired substrate folding by both bovine and archaeal TRiC complexes in vitro. These results together indicate that TRiC is a conserved target of arsenic inhibition in various biological systems.
| S-EPMC2954479 | biostudies-literature
Project description:Marine ingredients can contain relatively high levels of arsenic. The main aim of this study is to assess the hepatic toxicity of arsenic species in Atlantic salmon (Salmo salar) in vitro. Primary hepatocytes were isolated from six male Atlantic salmon and exposed for 48 h to establish dose-response curves for arsenite (AsIII) (0.1-3 μM) and for arsenosugar (AsSug) (5-250 μM). Regarding arsenite, results obtained indicated that the dose between 0.1 and 1 represented a marked threshold for effect. Very few genes were differentially expressed (N=5, p-adjust < 0.1) following AsIII 0.1 µM treatment compared to AsIII 1µM (N=2338 p-adjust < 0.01). Similar was observed for AsSug exposure where exposure to 50 µM resulted in 195 DEGs (p-adjust < 0.1) vs 6899 (p-adjust < 0.01) following AsSug 250µM exposure
2024-09-30 | GSE246522 | GEO
Project description:Exposure to high levels of arsenic in drinking water is associated with several types of cancers including lung, bladder and skin, as well as vascular disease and diabetes. Drinking water standards are based primarily on epidemiology and extrapolation from higher dose experiments, rather than measurements of phenotypic changes associated with chronic exposure to levels of arsenic similar to the current standard of 10ppb, and little is known about the difference between arsenic in food as opposed to arsenic in water. Measurement of phenotypic changes at low doses may be confounded by the effect of laboratory diet, in part because of trace amounts of arsenic in standard laboratory chows, but also because of broad metabolic changes in response to the chow itself. Finally, this series contrasts 8hr, 1mg/kg injected arsenic with the various chronic exposures, and also contrasts the acute effects of arsenic, dexamethasone or their combination. Male C57BL/6 mice were fed on two commercially available laboratory diets (LRD-5001 and AIN-76A) were chronically exposed, through drinking water or food, to environmentally relevant concentrations of sodium arsenite, or acutely exposed to dexamethasone. Experiment Overall Design: Male C57BL/6 mice, fed on two commercially available laboratory diets (LRD-5001 and AIN-76A), were chronically exposed through drinking water or food, to environmentally relevant concentrations of sodium arsenite. Another group animals, fed on the AIN 76A diet, was IP injected with dexamethasone (1 mg/kg), sodium arsenite (1mg/kg), both dexamethosone and arsenite, or saline alone.
2008-10-21 | E-GEOD-11056 | biostudies-arrayexpress
Project description:The present study used microarray expression profiling to determine the effects of embryonic arsenic exposure. Fertilized killifish (Fundulus heteroclitus) eggs were exposed to 0, 5, 15, or 25ppm arsenic as sodium arsenite. To examine differentially expressed genes, the microarrays were probed using RNA obtained from the control and 25ppm-exposed killifish just after hatching. No differences were noted in survival or hatching success between any of the groups. After analysis, a set of 332 genes was found to accurately distinguish between the control and 25ppm exposure groups. Expression of several of the genes (CDBP1, Arts1, FetB, and Fbp7) was quantified by qPCR in the lower exposure groups and at earlier time points to examine temporal and dose-responsive expression patterns. These results will enable us to better understand how arsenic impacts development. Killifish eggs were fertilized, divided into petri dishes containing 40 eggs (n=10 replicate petri dishes), and cultured until hatch in 0 or 25 ppm arsenic as sodium arsenite. Four to five hatchlings within each petri dish were pooled to obtain RNA. A total of 20 arrays were probed, 10 with RNA from control fish and 10 with RNA from the arsenic-exposed fish.
2011-07-31 | E-GEOD-29976 | biostudies-arrayexpress
Project description:Legumes, in interaction with resistant rhizobia, combined both moderate tolerance and accumulation of metal(loids) in roots, with the ability to grow without nitrogen supply (Pajuelo et al., 2011). This quality has attracted attention for phytostabilisation of polluted soils (Reichman, 2007). Physiological studies suggest that low arsenite concentrations lead to a decrease of nodulation process (Dary et al., 2010; Pajuelo et al., 2008). Moreover, Lafuente et al. (2010) described a reduction in the expression patterns of nodulins genes in the presence of arsenite. Nevertheless, a global transcriptomic analysis has never been approached. In order to decipher the genetic regulation underlying the arsenite effect on the model symbiotic interaction Medicago-Sinorhizobium, we have performed a meta-analysis of three different hybridizations. These compare transcriptomic profiles of roots cultivated under different treatments (M-125 M-5M arsenite, M-1rhizobia).
2014-12-08 | E-MTAB-1723 | biostudies-arrayexpress
Project description:Arsenic is an ubiquitous contaminant and a toxic metalloid which presents two main redox states in nature: arsenite [AsIII] and arsenate [AsV]. Arsenic resistance in Synechocystis sp. strain PCC 6803 is mediated by the arsBHC operon and two additional arsenate reductases encoded by the arsI1 and arsI2 genes. Here we describe the genome-wide responses in response to the presence of arsenate and arsenite in wild type and in mutants in the arsenic resistance system. Both forms of arsenic produced similar responses in the wild type strain including induction of several stress related genes and repression of energy generation processes. The responses observed in the arsB mutant strain were similar to the wild type in short term but were maintained in time while they were only transient in the wild type strain. In contrast, the responses observed in a strain lacking all arsenate reductases (the SARS12 strain) were somewhat different and included lower induction of genes involved in metal homeostasis and Fe-S cluster biogenesis. These results suggest that these two processes are targeted by arsenite in the wild type strain. Finally, analysis of the arsR mutant strain revealed that ArsR seems to only control 5 genes in the genome. Furthermore, over-expression of ArsB conferred hypersentivity to nickel, copper and cadmium in an arsR mutant strain. Analysis of genome-wide gene expression patterns in response to arsenic in WT and mutants involved in arsenic detoxification in the cyanobacterium Synechocystis sp PCC 6803. Cells treated with arsenate or arsenite for 1h. Details: WT cells were treated with 1 mM arsenite for 1 h and its expression profile compared to untreated cells (grown in BG11C media). The effects of arsenate were analyzed in the same way but using a modified BG11C media that constains 15% of the normal phosphate concentration (BG11C low phosphate). A reduction in the phosphate concentration in the media is essential to detect grow inhibition after arsenate addition. In the same way that for arsenite cells were treated with 50 mM arsenate for 1 h and their expression profile was compared to untreated cells. Expression profiles of mutant strains lacking arsB gene (SARSB strain; this strain is hypersensitive to arsenite because it lacks the arsenite exporter) or arsR gene (SARSR strain; this strain expresses the arsBHC constitutively) in control conditions and in response to arsenite addition were also analyzed. In addition the expression profiles of a mutant lacking arsenate reductases (SARS12 strain that has interrupted arsC, arsI1 and arsI2 genes; this strain is hypersensitive to arsenate) were analyzed in both control conditions and after addition of 50 mM arsenate.
2014-05-13 | E-GEOD-51383 | biostudies-arrayexpress
Project description:The present study used microarray expression profiling to determine the effects of embryonic arsenic exposure. Fertilized killifish (Fundulus heteroclitus) eggs were exposed to 0, 5, 15, or 25ppm arsenic as sodium arsenite. To examine differentially expressed genes, the microarrays were probed using RNA obtained from the control and 25ppm-exposed killifish just after hatching. No differences were noted in survival or hatching success between any of the groups. After analysis, a set of 332 genes was found to accurately distinguish between the control and 25ppm exposure groups. Expression of several of the genes (CDBP1, Arts1, FetB, and Fbp7) was quantified by qPCR in the lower exposure groups and at earlier time points to examine temporal and dose-responsive expression patterns. These results will enable us to better understand how arsenic impacts development.
2011-08-01 | GSE29976 | 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.
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2024-09-02 | BIOMD0000000547 | BioModels
Project description:The present study investigated arsenic’s effects on mummichogs (Fundulus heteroclitus), while also examining what role that gender or age of exposure might play. Adult male and female mummichogs were exposed to 172ppb, 575ppb, or 1,720ppb arsenic as sodium arsenite for 10 days immediately prior to spawning. No differences were noted in the number or viability of eggs between the groups, but there was a significant increase in deformities in the 1,720ppb arsenic exposure group. Total RNA from adult livers or 6-week-old juveniles was used to probe custom macroarrays for changes in gene expression. In females, 3% of the genes were commonly differentially expressed in the 172 and 575ppb exposure groups. In the males, between 1.1-3% of the differentially expressed genes were in common between the exposure groups. Several genes, including apolipoprotein, serum amyloid precursor, lysozyme, and tributyltin-binding protein, were commonly expressed in either a dose-responsive or dose-specific, but across genders, manner. These patterns of regulation were confirmed by QPCR. These findings will provide us with a better understanding of the effects of dose, gender, and exposure age on the response to arsenic.
2009-06-24 | GSE16771 | GEO