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Alterations in gene expression in Caenorhabditis elegans associated with exposure to several classes of toxic industrial chemicals/materials.

ABSTRACT: Effective toxicological testing of the vast number of new and existing chemicals currently in use will require efficient and cost effective methods. We evaluated the utility of a simple, low cost toxicity testing system employing the nematode Caenorhabditis elegans to identify toxicologically relevant changes in gene expression. The objective of this research is to determine genomic and proteomic responses in the model nematode C. elegans to exposures to representatives of several classes of toxic industrial chemicals/materials (TICs/TIMs). A total of 3 chemicals (acrylamide, cadmium chloride, and mercuric chloride) were used in these experiments. Affymetrix GeneChip for C. elegans was used to examine genome-wide responses in the 19,000+ genes of this model organism. Mid-vulval L4 worms were exposed to one of four concentrations of acrylamide, cadmium or mercury for 4h and 8h. Exposures were performed in triplicate.

ORGANISM(S): Caenorhabditis elegans

SUBMITTER: John Lewis

PROVIDER: E-GEOD-42592 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Alterations in gene expression in Caenorhabditis elegans associated with exposure to several classes of toxic industrial chemicals/materials.

Project description:Effective toxicological testing of the vast number of new and existing chemicals currently in use will require efficient and cost effective methods. We evaluated the utility of a simple, low cost toxicity testing system employing the nematode Caenorhabditis elegans to identify toxicologically relevant changes in gene expression. The objective of this research is to determine genomic and proteomic responses in the model nematode C. elegans to exposures to representatives of several classes of toxic industrial chemicals/materials (TICs/TIMs). A total of 3 chemicals (acrylamide, cadmium chloride, and mercuric chloride) were used in these experiments. Affymetrix GeneChip for C. elegans was used to examine genome-wide responses in the 19,000+ genes of this model organism.

2012-11-28 | GSE42592 | GEO

Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: atrazine

Project description:Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to atrazine (AZ). For AZ, the physiological mode of action predicted by DEBtox was increased cost for maintenance. The transcriptional analysis demonstrated that this increase resulted from effects on DNA integrity as indicated by changes in the expression of genes chromosomal repair. Our results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes. Adults of C. elegans strain GE-31 exposed as biological replicate groups (approx 10,000) to a control and 4 concentrations of atrazine from L1 stage. Replicate populations were sampled 12 hours after the on-set of egg laying and hybridised against a common reference for purposes of normalisation. All experiments were conducted following a reference design with the reference sample compiled from a mixture of RNA extracted from control and cadmium-, fluoranthene-, atrazine- and copper-exposed worms from L1, L4 and adult life-stages. Use of this reference was intended to provide optimal coverage of the spotted genes.

2010-03-23 | E-GEOD-21008 | biostudies-arrayexpress

Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: cadmium

Project description:Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to cadmium. For Cd, the physiological mode of action as indicated by DEBtox model fitting was an effect on energy assimilation from food, suggesting that the transcriptional response to exposure should be dominated by changes in the expression of transcripts associated with energy metabolism and the mitochondria. While evidence for effect on genes associated with energy production were seen, an ontological analysis also indicated an effect of Cd exposure on DNA integrity and transcriptional activity. Our results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes. Adults of C. elegans strain GE-31 exposed as biological replicate groups (approx 10,000) to a control and 4 concentrations of cadmium from L1 stage. Replicate populations were sampled 12 hours after the on-set of egg laying and hybridised against a common oligonucleotide reference for purposes of normalisation. All experiments were conducted following a reference design with the reference sample compiled from a mixture of RNA extracted from control and cadmium-, fluoranthene-, atrazine- and copper-exposed worms from L1, L4 and adult life-stages. Use of this reference was intended to provide optimal coverage of the spotted genes.

2010-05-05 | E-GEOD-21010 | biostudies-arrayexpress

Transcription profiling of Caenorhabditis elegans treated with Dichlorvos and fenamiphos, to investigate it as a genomic model for toxicology

Project description:Effective toxicological testing of the vast number of new and existing chemicals currently in use will require efficient and cost effective methods. We evaluated the utility of a simple, low cost toxicity testing system employing the nematode Caenorhabditis elegans to identify toxicologically relevant changes in gene expression. Dichlorvos and fenamiphos, which are organophosphorous pesticides that inhibit acetylcholinesterase were chosen as model toxicants to test the usefulness of the C. elegans toxicity testing system, and mefloquine, which appears to perturb neuronal Ca++ homeostasis, provided an out-group for analysis. Experiment Overall Design: Concentrations of dichlorvos, fenamiphos, or mefloquine sufficient to prevent the development of 10%, 50%, or 90% of mid-vulval L4 worms to the early gravid adult stage at 24 h after exposure were determined in range finding experiments. For definitive experiments, mid-vulval L4 worms were exposed to one of the foregoing concentrations of dichlorvos, fenamiphos, or mefloquine for 8h. Exposures were performed in triplicate.

2009-06-24 | E-GEOD-12298 | biostudies-arrayexpress

Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans

Project description:This SuperSeries is composed of the following subset Series: GSE21008: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: atrazine GSE21010: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: cadmium GSE21011: Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: fluoranthene Refer to individual Series

2010-03-23 | E-GEOD-21012 | biostudies-arrayexpress

Linking toxicant physiological mode of action with induced gene expression changes in Caenorhabditis elegans: fluoranthene

Project description:Physiologically based modelling using DEBtox (dynamic energy budget in toxicology) and transcriptional profiling were used in Caenorhabditis elegans to identify how physiological modes of action, as indicated by effects on system level resource allocation were associated with changes in gene expression following exposure to fluoranthene (FA). DEBtox modelling showed an effect of FA on costs for growth and reproduction (i.e. for production of new and differentiated biomass). The microarray analysis supported this effect, showing an effect of FA on protein integrity and turnover that would be expected to have consequences for rates of somatic growth. Our results have established that outputs from process based models and transcriptomics analyses can help to link mechanisms of action of toxic chemicals with resulting demographic effects. Such complimentary analyses can assist in the categorisation of chemicals for risk assessment purposes. Adults of C. elegans strain GE-31 were exposed as biological replicate groups (approx 10,000) to a control and 4 concentrations of fluoranthene from L1 stage. Replicate populations were sampled 12 hours after the on-set of egg laying and hybridised against a common oligonucleotide reference for purposes of normalisation. All experiments were conducted following a reference design with the reference sample compiled from a mixture of RNA extracted from control and cadmium-, fluoranthene-, atrazine- and copper-exposed worms from L1, L4 and adult life-stages. Use of this reference was intended to provide optimal coverage of the spotted genes.

2010-05-05 | E-GEOD-21011 | biostudies-arrayexpress

Effects of ccf-1 RNAi on C. elegans response to cadmium and acrylamide

Project description:In a genome-wide RNAi screen to identify activators of numr-1, a cadmium responsive gene involved in RNA splicing regulation, we isolated ccf-1 as a gene that is required for cadmium-induced numr-1 activation. The ccf-1 gene encodes a deadenylase within the CCR4-NOT complex that generally serves to suppress gene expression by initiating mRNA degradation. However, a role for ccf-1 as a positive regulator of stress-induced gene expression remains to be characterized. Silencing of ccf-1 inhibits various classes of cadmium-inducible genes including several glutathione-s-transferase (gst) and heat shock protein genes. RNAi knockdown of ccf-1 significantly reduces lifespan and decreases survival in cadmium, implicating a role for ccf-1 in aging and stress protection. The ccf-1 gene is also required for resistance against acrylamide with RNAi depletion of ccf-1 inhibiting acrylamide-induced gst induction, decreasing survival in acrylamide stress, and increasing C. elegans sensitivity to acrylamide-induced neurodegeneration. Using RNA-sequencing, we observed that ccf-1 regulates ~28-35% of all genes induced by cadmium (500 out of 1802 DEG) or acrylamide (296 out of 851 DEG) by >2-fold. Clustering analysis of ccf-1 dependent cadmium or acrylamide up-regulated genes indicate significant enrichment to glutathione and cytochrome P450 metabolism, suggesting a central role for ccf-1 in regulating antioxidant defense across different stressors. Using a CCF-1::GFP translational reporter, we find that CCF-1 is broadly expressed in the intestine, muscle, and hypodemis. Interestingly, CCF-1::GFP strongly localizes to the intestinal nuclei, implicating a potential nuclear role for CCF-1 in transcriptional regulation that is distinct for its deadenylase function in the cytoplasm

2023-02-17 | GSE194057 | GEO

Dynamic changes of histone H3 marks during Caenorhabditis elegans lifecycle revealed by middle-down proteomics

Project description:We applied a middle-down proteomics strategy for large scale protein analysis during in vivo development of Caenorhabditis elegans. We characterized post-translational modifications (PTMs) on histone H3 N-terminal tails at eight time points during the C. elegans lifecycle, including embryo, larval stages (L1 to L4), dauer and L1/L4 post dauer. Histones were analyzed by our optimized middle-down protein sequencing platform using high mass accuracy tandem mass spectrometry. This allows quantification of intact histone tails and detailed characterization of distinct histone tails carrying co-occurring PTMs. We measured temporally distinct combinatorial PTM profiles during C. elegans development. We show that the doubly modified form H3K23me3K27me3, which is rare or non-existent in mammals, is the most abundant PTM in all stages of C. elegans lifecycle. The abundance of H3K23me3 increased during development and it was mutually exclusive of the active marks H3K18ac, R26me1 and R40me1, suggesting a role for H3K23me3 in to silent chromatin. We observed distinct PTM profiles for normal L1 larvae and for L1-post dauer larvae, or L4 and L4 post-dauer, suggesting that histone PTMs mediate an epigenetic memory that is transmitted during dauer formation. Collectively, our data describe the dynamics of histone H3 combinatorial code during C. elegans lifecycle and demonstrate the feasibility of using middle-down proteomics to study in vivo development of multicellular organisms.

2015-11-02 | PXD002525 | Pride

wt vs daf-2 C. elegans protein turnover

Project description:Most aging hypotheses revolve around the accumulation of some sort of damage resulting in gradual physiological decline and ultimately death. Avoiding protein damage accumulation by enhanced turnover should slow down the aging process and extend lifespan. However, lowering translational efficiency extends rather than shortens lifespan in C. elegans. We studied turnover of individual proteins in the conserved Insulin/Insulin-like Growth Factor (IGF-1) receptor mutant daf-2 by combining Stable Isotope Labeling by Nitrogen-15 in Caenorhabditis elegans and LC-MS/MS. Intriguingly, the majority of proteins displayed prolonged half-lives in daf-2, while others remained unchanged, signifying that longevity is not supported by high protein turnover. This slow-down of protein turnover was most prominent for components of the translation machinery and mitochondria. In contrast, the high turnover of lysosomal hydrolases and very low turnover of cytoskeletal proteins remained largely unchanged in daf-2. The slow-down of protein dynamics and decreased abundance of the translational machinery may point at the importance of anabolic attenuation in lifespan extension as suggested by the hyperfunction theory.

2016-09-27 | PXD002317 | Pride

C. elegans gene expression in response to Y. pestis KIM5 infection

Project description:The response of the nematode C. elegans to Y. pestis infection was evaluated by gene expression profiling. A synchronized population of nematodes were exposed to Y. pestis KIM5 for 24h. Transcript levels from Y. pestis-treated animals were compared with animals maintained on relatively nonpathogenic E. coli OP50 for 24h. Three independent RNA isolations were performed following exposure to either Y. pestis KIM5 or E. coli OP50. Exposures to the different pathogens were performed in parallel for each replicate isolation.

2010-02-22 | E-GEOD-20053 | biostudies-arrayexpress

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