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

ABSTRACT: 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.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE21008 | GEO | 2010/03/23

SECONDARY ACCESSION(S): PRJNA129655

REPOSITORIES: GEO

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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

2010-03-23 | GSE21010 | GEO

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

2010-03-23 | GSE21011 | GEO

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

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

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

Candida auris proteomic profiling

Project description:In this study, we designed a novel antifungal agent, PQA-Az-13 that demonstrated antifungal activity against C. auris biofilms. Cellular proteomics indicated that PQA-Az-13 partially or completely inhibited numerous enzymatic proteins in C. auris biofilms, particularly those involved in both amino acid biosynthesis and metabolism processes, as well as in general energy-producing processes. Due to its hydrophobic nature and limited aqueous solubility, PQA-Az-13 was encapsulated in cationic liposomes and characterized by biophysical and spectral techniques. PQA-Az-13 liposomes demonstrated enhanced antifungal activity levels against both C. auris in in vitro biofilms and ex vivo skin colonization models.

2023-12-07 | PXD046911 | Pride

The zingerone analog, acetyl zingerone, bolsters matrisome synthesis, inhibits MMPs, and represses IL-17A target gene expression [Experiment 2]

Project description:Zingerone (Z) is a phenolic alkanone derived from natural sources with anti-inflammatory and antioxidant effects. Acetyl zingerone (AZ) is a newly designed molecule that shares structural features with Z but is expected to have improved stability and antioxidant function. This study utilized microarrays to compare effects of Z and AZ on gene expression in reconstituted human epidermis. Both Z and AZ increased Notch pathway gene expression (NOTCH1, MAML3) and decreased expression of genes linked to extracellular matrix disassembly (MMP3, CTSV) and reactive oxygen species metabolism (PMAIP1, ARG2). Although Z and AZ each inhibited in vitro MMP-1, MMP-3 and MMP-12 activity, inhibition of MMP-3 and MMP-12 was greater with AZ. Moreover, AZ led to more consistent increases in the expression of genes encoding collagens (COL11A2), proteoglycans (VCAN) and ECM glycoproteins (SPARC). Finally, AZ opposed gene expression patterns associated with fibroblast senescence, keratinocyte differentiation, and IL-17A stimulation. These effects were AZ-specific and not replicated by Z. These results show that AZ improves extracellular matrix integrity with retinoid-like effects on differentiation and inflammation. Our findings provide rationale for clinical studies to understand benefits of AZ in the treatment or prevention of skin aging, or potentially, as a treatment for other human skin diseases. Microarray analyses was performed to characterize global gene expression responses to acetyl zingerone (AZ) (50 μg/ml) in EpiDerm FT (RHE) tissue cultures.

2019-09-26 | GSE133339 | GEO

The zingerone analog, acetyl zingerone, bolsters matrisome synthesis, inhibits MMPs, and represses IL-17A target gene expression [Experiment 1]

Project description:Zingerone (Z) is a phenolic alkanone derived from natural sources with anti-inflammatory and antioxidant effects. Acetyl zingerone (AZ) is a newly designed molecule that shares structural features with Z but is expected to have improved stability and antioxidant function. This study utilized microarrays to compare effects of Z and AZ on gene expression in reconstituted human epidermis. Both Z and AZ increased Notch pathway gene expression (NOTCH1, MAML3) and decreased expression of genes linked to extracellular matrix disassembly (MMP3, CTSV) and reactive oxygen species metabolism (PMAIP1, ARG2). Although Z and AZ each inhibited in vitro MMP-1, MMP-3 and MMP-12 activity, inhibition of MMP-3 and MMP-12 was greater with AZ. Moreover, AZ led to more consistent increases in the expression of genes encoding collagens (COL11A2), proteoglycans (VCAN) and ECM glycoproteins (SPARC). Finally, AZ opposed gene expression patterns associated with fibroblast senescence, keratinocyte differentiation, and IL-17A stimulation. These effects were AZ-specific and not replicated by Z. These results show that AZ improves extracellular matrix integrity with retinoid-like effects on differentiation and inflammation. Our findings provide rationale for clinical studies to understand benefits of AZ in the treatment or prevention of skin aging, or potentially, as a treatment for other human skin diseases. Microarray analyses was performed to characterize global gene expression responses to zingerone (Z) (50 μg/ml) in EpiDerm FT (RHE) tissue cultures.

2019-09-26 | GSE133338 | GEO

Alizarin Red perturbs skeletal patterning and biomineralization via Catalase inhibition

Project description:Alizarin Red (AZ) is an anthraquinone dye that is commonly used in histological studies and textiles. Exposure to AZ results in morphological perturbations in several species, including rats, frogs, and dogs; however, the mechanisms by which AZ has these effects is largely unexplored, and little is known about its effect on development. We have previously shown that AZ is teratogenic to sea urchin larvae, and that AZ was the only calcium-binding mineralization marker among five tested that perturbed skeletal patterning. Here, we characterize these defects further and demonstrate that embryos exposed to AZ have abnormal skeletal element rotation, branching, and bending. Immunostains and polychrome labeling revealdelayed migration of primary mesenchyme cells and initiation of biomineralization. Although gross ectodermal dorsal-ventral specification, ciliary band restriction, and neuronal specification occur normally in most AZ-treated embryos, we find abnormal patterning and connectivity of the serotonergic neurons. Temporal transcriptomics comparisons confirm delayed development and implicate changes neuron-related GO terms with AZ treatment. Particle velocity imaging experiments show that ciliary beating normally directs fluid flow into the larval mouth, while AZ treatment perturbs the normal pattern of vortices and redirects flow away from the mouth. Finally, we show that the effects of AZ on skeletal patterning are largely due to the inhibition of catalase and subsequent elevation of reactive oxygen species. Specifically, catalase knockdown and transient hydrogen peroxide treatment are each sufficient to phenocopy the hallmark AZ skeletal patterning defects. This study is the first to define the consequences of AZ and its effects on neuronal function and catalase activity, with consequent impacts on development, skeletal patterning, and biomineralization.

2024-07-01 | GSE270804 | GEO

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