Transcriptomic implications of low herbicide concentrations in hepatic cells: Insights into the individual and combined effects of 2,4-D, glyphosate, and AMPA
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ABSTRACT:
PROVIDER: PRJNA1241787 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32850969_1.fastq.gz | Fastqsanger.gz | |||
| SRR32850969_2.fastq.gz | Fastqsanger.gz | |||
| SRR32850970_1.fastq.gz | Fastqsanger.gz | |||
| SRR32850970_2.fastq.gz | Fastqsanger.gz | |||
| SRR32850971_1.fastq.gz | Fastqsanger.gz |
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Project description:Glyphosate and 2,4-D are among the most widely used herbicides globally, leading to environmental presence, food contamination, and human contact. Investigations based on current toxicological limits or populational-based herbicide exposures are warranted, and in vitro bioassays provide useful tools for toxicological screening. Thus, this study evaluated the transcriptomic implications of non-cytotoxic exposures to glyphosate, its metabolite aminomethylphosphonic acid (AMPA), or 2,4-D - or to their mixes - on hepatic cells. The half maximal effective concentration (IC50) of each herbicide was calculated (cell viability) in human hepatic C3A cells and 1000-fold lower concentrations were used for transcriptomic analysis (RNA-Seq) after 48h exposure, resembling current toxicological limits and considering herbicide water levels (glyphosate: 0.95 µg/mL; AMPA: 3.7 µg/mL; 2,4-D: 0.56 µg/mL). Glyphosate exposure enriched MAPK-related biological processes (upregulated TNF, FOS, IGF1, and PDGFB), and downregulated genes associated with lipid metabolism (CD36 and PPARA). Many AMPA exposure-related differentially expressed genes (DEGs, such as PFKFB3, HK2, and ALDOA) were associated with glucose metabolic pathways. Glyphosate and its metabolite yielded a common molecular signature, as illustrated by principal component analysis and the function of 212 shared DEGs. The exposure to 2,4-D was associated with the JNK cascade and the solute carrier family annotations. The herbicide mixtures had a discrete effect on enhancing the impact of individual herbicides, although important epithelial-mesenchymal transition genes were exclusively modified by the mixes (COL11A2, LOXL3, SNAI1). Altogether, our data reveals new perspectives on the short-term molecular effects of herbicide exposure in liver cells, emphasizing potential avenues for further exploration.
2025-03-25 | GSE292868 | GEO
Project description:Using whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to glyphosate (Roundup Original) herbicde that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme and thus disrupts aromaticamino acid biosynthesis. Few genes related to defense and secondary metabolism were altered. Experiment Overall Design: Surfactant (preference 0.25%) treated plants were used as carrier control group and EC50 concentration of glyphosate was used as the herbicide treatment group. Each of the control and treatment group consisted of 3 biological replicates and each biological replicates comprised leaves from 10 individual plants. RNA was extracted at 24h post treatment to study the transcriptional alterations caused by the herbicide treatment.
2009-08-07 | E-GEOD-8927 | biostudies-arrayexpress
Project description:This project aimed to investigate the effects of glyphosate-based herbicide Roundup LB Plus on bacteria. For this, ten environmental strains of Salmonella enterica were exposed to the increasing concentrations of Roundup over several passages to obtain Roundup-resistant mutants. Four stable re-sequenced resistant mutants and their respective ancestors were characterized by global proteomics in the presence and absence of sub-inhibitory (1/4xMIC) concentrations of the herbicide. By comparing the proteomes of the Roundup-challenged ancestors with constitutive non-challenged ancestors, it became possible to deepen the understanding of how Roundup stress affects naïve bacteria. Similarly, comparing Mutants versus Ancestors in the absence of Roundup allowed to understand how Roundup resistance constitutively affects bacterial physiology, while the comparison of Roundup-challenged mutants versus constitutive mutants helped improve the understanding of the inducible responses in the resistant background.
2020-09-22 | PXD019463 | Pride
Project description:Using whole genome microarray (Affymetrix ATH1) we studied the transcriptional response of Arabidopsis thaliana to glyphosate (Roundup Original) herbicde that inhibits 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme and thus disrupts aromaticamino acid biosynthesis. Few genes related to defense and secondary metabolism were altered. Keywords: 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) inhibiting herbicide stress response
2009-07-22 | GSE8927 | GEO
Project description:In order to evaluate the molecular effects of Roundup at a concentration at which no morphological effects were identified, RNA extracted from Roundup-treated A. nidulans cultures were subjected to a global gene expression profiling using a custom agilent microarray (8 × 15 K format), for which the reproducibility, specificity and sensitivity was described previously (Delomenie et al., Curr Genet 2016 Nov;62(4):897-910. PMID: 27038308). This data is published in Mesnage R, Oestreicher N, Poirier F, Nicolas V, Boursier C, Vélot C. (2020) Transcriptome profiling of the fungus Aspergillus nidulans exposed to a commercial glyphosate-based herbicide under conditions of apparent herbicide tolerance. Environmental Research. Available online 7 January 2020, 109116. https://doi.org/10.1016/j.envres.2020.109116
2020-01-08 | GSE95241 | GEO
Project description:The synthetic auxin 2,4-dichlorophenoxyacetic acid (2,4-D) functions as an agronomic weed control herbicide. High concentrations of 2,4-D induce plant growth defects, particularly leaf epinasty and stem curvature. Although the 2,4-D phenotype is associated with ROS production, little is known about ROS-dependent signalling. In this study, by using T-DNA Arabidopsis mutants to silence peroxisomal acyl CoA oxidase 1 (acx1-2), we identified ACX1 as one of the main sources of ROS production and as partly the cause of the epinasty phenotype following the application of 2,4-D. Transcriptomic analyses of WT plants after treatment with 2,4-D revealed a ROS-related peroxisomal footprint in early plant responses, while other organelles, such as mitochondria and chloroplasts, are involved in later responses. Interestingly, a group of ACX1-dependent transcripts in plant responses to 2,4-D, previously associated with epinasty, is related to auxin biosynthesis, metabolism and signalling. We found that protein AUXIN SIGNALING F-BOX 3 (AFB3), a component of SCF (ASK-cullin-F-box) E3 ubiquitin ligase complexes, which functions as an auxin receptor and mediates Aux/IAA proteasomal degradation, acts downstream of ACX1 and is involved in the epinasty phenotype induced by 2,4-D. We also found that protein degradation associated with ubiquitin E3-RING and E3-SCF-FBOX in ACX1-dependent signalling in plant responses to 2,4-D is significantly regulated over longer treatment periods.
2021-12-01 | GSE179303 | GEO
Project description:Background: Herbicides are environmental contaminants that have gained much attention due to the potential hazards they pose to human health. Glyphosate, the active ingredient in many commercial herbicides, is the most heavily applied herbicide worldwide. The recent rise in glyphosate application to corn and soy crops correlates positively with increased death rates due to Alzheimer's disease and other neurodegenerative disorders. Glyphosate has been shown to cross the blood-brain barrier in in vitro models, but has yet to be verified in vivo. Additionally, reports have shown that glyphosate exposure increases pro-inflammatory cytokines in blood plasma, particularly TNFα. Methods: Here, we examined whether glyphosate infiltrates the brain and elevates TNFα levels in 4-month-old C57BL/6J mice. Mice received either 125, 250, or 500 mg/kg/day of glyphosate, or a vehicle via oral gavage for 14 days. Urine, plasma, and brain samples were collected on the final day of dosing for analysis via UPLC-MS and ELISAs. Primary cortical neurons were derived from amyloidogenic APP/PS1 pups to evaluate in vitro changes in Aβ40-42 burden and cytotoxicity. RNA sequencing was performed on C57BL/6J brain samples to determine changes in the transcriptome. Results: Our analysis revealed that glyphosate infiltrated the brain in a dose-dependent manner and upregulated TNFα in both plasma and brain tissue post-exposure. Notably, glyphosate measures correlated positively with TNFα levels. Glyphosate exposure in APP/PS1 primary cortical neurons increases levels of soluble Aβ40-42 and cytotoxicity. RNAseq revealed over 200 differentially expressed genes in a dose-dependent manner and cell-type-specific deconvolution analysis showed enrichment of key biological processes in oligodendrocytes including myelination, axon ensheathment, glial cell development, and oligodendrocyte development. Conclusions: Collectively, these results show for the first time that glyphosate infiltrates the brain, elevates both the expression of TNFα and soluble Aβ, and disrupts the transcriptome in a dose-dependent manner, suggesting that exposure to this herbicide may have detrimental outcomes regarding the health of the general population.
2024-01-15 | GSE253299 | GEO
Project description:Resistance to the phenoxy synthetic auxin herbicide 2,4-D is conferred by a deletion mutation in the degron tail of IAA2. An RNA-Seq experiment was used to assemble a reference transcriptome for the weed species Sisymbrium orientale, to quantify gene expression, and to identify sequence variants in the alignments. A 27 bp deletion was identified in the IAA2 gene. Forward genetics supported the role of this deletion mutation in resistance. The IAA2 deletion allele was transformed into Arabidopsis thaliana to confirm that it conferred 2,4-D resistance.
2020-10-08 | GSE159202 | GEO
Project description:Despite all debates about its safe use, glyphosate still is the most widely applied active ingredient in herbicide products with renewed approval in the European Union until 2033. Non-target organisms are commonly exposed to glyphosate as a matter of its mode of application, with its broader environmental and biological impacts remaining under investigation. Glyphosate displays structural similarity to phosphoenolpyruvate (PEP), thereby competitively inhibiting the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS), crucial for the synthesis of aromatic amino acids in plants, fungi, bacteria, and archaea. The majority of microbes, including the gut bacterium Escherichia coli (E. coli), possess a glyphosate-sensitive class I EPSPS, making them vulnerable to glyphosate's effects. Yet, little is known about glyphosate’s interactions with other bacterial proteins or its broader modes of action at the proteome level. Here, we employed a quantitative proteomics and thermal proteome profiling (TPP) approach, to identify novel protein binding partners of glyphosate in the E. coli proteome. Glyphosate exposure significantly altered amino acid synthesizing pathways, including increased abundance in shikimate pathway proteins, suggesting a compensatory mechanism. Extracellular riboflavin concentrations were elevated upon glyphosate exposure, while intracellular levels remained stable. Thermal proteome profiling indicated an effect of glyphosate on the thermal stability of certain proteins beyond the target enzyme EPSPS, including AroH and ProA. An elevated structural similarity between the substrates of the interaction candidates and glyphosate, similar to the competitive binding between PEP and glyphosate at the EPSPS, could be a reason for their interaction with the herbicide. Overall, glyphosate induced metabolic disturbances in E. coli, extending beyond its primary target, thereby providing new insights into glyphosate's broader impact on microbial systems.
2025-01-02 | PXD055134 | Pride
Project description:Small RNAs have emerged as a promising new type of biomarker to monitor health status and track the development of diseases. Here we report changes in the levels of small RNAs in the liver of rats exposed to a mixture (MIX) of six pesticides frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole), and glyphosate (G50) (50 mg/kg bw/day), or its representative EU commercial herbicide formulation Roundup MON 52276 (R50) at the same glyphosate equivalent doses in comparison to a control group (CON).
2022-03-09 | GSE182559 | GEO