Folate deficiency enhances arsenic effects on ODC mouse skin gene expression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE8733 | GEO | 2007/08/10
SECONDARY ACCESSION(S): PRJNA101993
REPOSITORIES: GEO
Similar Datasets
Project description:We demonstrate that expression of key markers of keratinocyte differentiation is suppressed by exposure to sodium arsenite. Folate deficiency exacerbates this effect. In addition, cancer-related cell movement genes, and growth and proliferation genes are altered. Several redox-sensitive transcription factors are implicated in mediating these gene expression changes due to arsenic treatment and folate deficiency. Experiment Overall Design: K6/ODC mice were maintained on either a folate deficient or folate sufficient diet and exposed to 0, 1, or 10 ppm sodium arsenite in the drinking water for 30 days. Total RNA was isolated from skin samples and gene expression analyzed using Affymetrix Mouse 430 2.0 GeneChips. Data from 24 samples, with four mice in each of the six treatment groups, were analyzed.
2008-06-16 | E-GEOD-8733 | biostudies-arrayexpress
Project description:Folate deficiency, arsenic exposure, and gamma-IR are known developmental toxicants and have carcinogenic effects. The mechanism by which IR is known, but the effect of arsenic or folate deficiency remains unclear. Their effect may be mediated by epigenetic alterations, leading to miRNA expression changes, and this experiment examined this hypothesis We used microarrays to detail the miRNA expression profiles of TK6 cells treated with 2 uM sodium arsenite for 6 days, folate-deficient media for 6 days, or 2.5 Gy IR exposure either acutely at 4 hours post exposure or long-term at 6 days post exposure, as well as requiste controls, all in biological triplicate. Keywords: exposure differences
2006-11-15 | GSE6020 | GEO
Project description:Folate deficiency, arsenic exposure, and gamma-IR are known developmental toxicants and have carcinogenic effects. The mechanism by which IR is known, but the effect of arsenic or folate deficiency remains unclear. Their effect may be mediated by epigenetic alterations, leading to miRNA expression changes, and this experiment examined this hypothesis We used microarrays to detail the miRNA expression profiles of TK6 cells treated with 2 uM sodium arsenite for 6 days, folate-deficient media for 6 days, or 2.5 Gy IR exposure either acutely at 4 hours post exposure or long-term at 6 days post exposure, as well as requiste controls, all in biological triplicate. Keywords: exposure differences TK6, were cultured in standard RPMI 1640 (Invitrogen Inc., Gaithersburg, MD) or folate-deficient RPMI 1640 (Invitrogen). Growth media was supplemented with 10% fetal bovine serum (Invitrogen) and 1% penicillin-streptomycin; dialyzed fetal bovine serum (Invitrogen) was added to the folate-deficient medium in order to eliminate folic acid in the serum. For controls, folate-deficiency, arsenic exposure, and 6-day ?-IR exposure groups, 106 cells were diluted into 50ml of appropriate growth media. For the 4-hour post-?-IR exposure group, 107 cells were diluted into 50ml of growth media. For the arsenic exposed group, sodium arsenite was added to the media to a concentration of 2 ?M. For the ?-IR exposure groups, cells were diluted and allowed to incubate for 4 hours prior to irradiation treatment, and were exposed at a dose rate of 86.76 rad/min to a final dose of 2.5 Gy using a Philips MGC-40 X-ray source. Following exposure, cells were returned to the incubator. After fours hours, the short-term post-??-IR exposure group was collected for RNA isolation, as well as a mock (control) group. All experimental and control conditions were performed in triplicate. For all other groups, cells were cultured for 6 days, with the media changed and renewed, with the appropriate treatment, on day 3.
2010-06-09 | E-GEOD-6020 | 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: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: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: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: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.
2014-05-13 | GSE51383 | GEO
Project description:Purpose: To determine the effects of sodium arsenite in male mice on adaptive thermogenesis. Methods: Male C57BL/6J mice were exposed to sodium arsenite in drinking water at 300 parts per billion (ppb) for 9 weeks Findings: Arsenic-treated mice experienced significantly decreased metabolic heat production when acclimated to chronic cold tolerance testing, as evidenced by indirect calorimetry, despite no change in physical activity. Arsenic exposure increased total fat mass, and unilocular lipid droplet size in both subcutaneous inguinal white adipose tissue (iWAT) and brown adipose tissue (BAT). Conclusion: Chronic arsenic exposure impacts the mitochondria of thermogenic tissues involved in energy expenditure and glucose regulation, providing novel mechanistic evidence for arsenic’s role in metabolic pathologies.
2020-01-01 | GSE134982 | 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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BIOMD0000000547.
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2014-09-04 | BIOMD0000000547 | BioModels