Differential gene expression profiling in response to paraquat using a Drosophila Parkinson's disease model
Ontology highlight
ABSTRACT:
ORGANISM(S): Drosophila melanogaster
PROVIDER: GSE135919 | GEO | 2019/09/16
REPOSITORIES: GEO
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Project description:Cigarette smoking is associated with reduced risk of developing Parkinson’s disease (PD). To identify genes that interact with nicotine/smoking, we performed hypothesis-free genome-wide experiments in a paraquat-induced Drosophila model and in a case-control study of PD. We demonstrated that nicotine extends life-span in paraquat-treated Drosophila (P=4E-30). Brain tissue from flies treated with combinations of paraquat and nicotine revealed elevated expression of CG14691 with paraquat which was restored with nicotine co-treatment (P(interaction)=2E-11, P(FDR-adjusted)=4E-7). Independently, variants in the 5’ region of SV2C, a human ortholog of CG14691, gave the strongest signal for interaction with smoking (P(interaction)=9E-8). The effect of smoking on PD risk varied six-fold by SV2C genotype (P(heterogeneity)=4E-10). Moreover, SV2C variants identified here were associated with SVC2 gene-expression in the HapMap data. Present results suggest synaptic vesicle protein SV2C plays a role in PD pathogenesis, and that the SV2C genotype may be useful for clinical trials of nicotine for treating PD. Drosophila female heads were dissected after exposure to plain food, food with paraquat, food with nicotine, or food with both paraquat and nicotine, and genome-wide expression was quantified using Affymetrix microarrays. 20 heads were pooled per replicate, with each treatment in triplicate, and all flies were dissected at the same timepoint, after 10 days of pretreatment (with 0.1 mg/ml nicotine or no nicotine, depending on treatment group), and then a further 6 days of treatment with either 5 mM paraquat or no paraquat, continuing on the pretreatment dose of nicotine. One biological replicate in the paraquat-only group showed RNA degradation and was not included in the normalization or subsequent analyses.
2012-09-05 | E-GEOD-35930 | biostudies-arrayexpress
Project description:We use RNAseq to compare the transcriptomes of wild type and cells treated with 2.5 mM paraquat (PQ) for 8 hr. We find that PQ treatment results in changes in the transcripts for hundreds of genes. A notable subset of PQ-induced transcripts encodes proteins activated by the retrograde response pathway. This pathway is activated by ETC dysfunction and regulates carbohydrate metabolism to increase synthesis of biosynthetic intermediates through pathways including the TCA cycle, glutamine biosynthetic pathway, and isocitrate metabolism. Transcripts encoding oxidative stress response proteins (e.g. amino acid and iron transporters and siderophores) are also more abundant in PQ-treated cells.
2020-05-19 | GSE150804 | GEO
Project description:Profiled the effect of oxidative stress on gene expression in the heads of adult Drosophila. The flies were fed sucrose with 15mM paraquat (experimental condition) or regular sucrose (control condition) for 30 hours, before harvesting at adult d3. Keywords = oxidative stress Keywords = paraquat Keywords: dose response
2004-01-18 | GSE827 | GEO
Project description:Profiled the effect of oxidative stress on gene expression in the heads of adult Drosophila. The flies were fed sucrose with 15mM paraquat (experimental condition) or regular sucrose (control condition) for 30 hours, before harvesting at adult d3.
2008-06-16 | E-GEOD-827 | biostudies-arrayexpress
Project description:Cigarette smoking is associated with reduced risk of developing Parkinson’s disease (PD). To identify genes that interact with nicotine/smoking, we performed hypothesis-free genome-wide experiments in a paraquat-induced Drosophila model and in a case-control study of PD. We demonstrated that nicotine extends life-span in paraquat-treated Drosophila (P=4E-30). Brain tissue from flies treated with combinations of paraquat and nicotine revealed elevated expression of CG14691 with paraquat which was restored with nicotine co-treatment (P(interaction)=2E-11, P(FDR-adjusted)=4E-7). Independently, variants in the 5’ region of SV2C, a human ortholog of CG14691, gave the strongest signal for interaction with smoking (P(interaction)=9E-8). The effect of smoking on PD risk varied six-fold by SV2C genotype (P(heterogeneity)=4E-10). Moreover, SV2C variants identified here were associated with SVC2 gene-expression in the HapMap data. Present results suggest synaptic vesicle protein SV2C plays a role in PD pathogenesis, and that the SV2C genotype may be useful for clinical trials of nicotine for treating PD.
2012-09-05 | GSE35930 | GEO
Project description:Despite its banishment in several countries, Paraquat (PQ) is still one of the most commonly used herbicides in agriculture. This compound is known to induce damaging effects on human or animal brain cells such as glial cells or neurons through biological processes as redox by generation of Reactive Oxygen Species (ROS). This specific perturbation has already proven its association for increasing the risk of developing a long-term brain impairment in in vitro and in vivo studies using brain cells. However, there is few evidence of PQ effect on Human Brain Microvascular Endothelial Cells (HBMECs), a particular cell type acting as a macromolecule permeability regulator in the Blood-Brain Barrier (BBB). The present study aimed at unraveling biological mechanisms associated to the exposition of 1, 10 and 100 µM of PQ for 24h on HBMECs. High-throughput mass spectrometry-based proteomics using data-independent acquisition (DIA) was applied. Biological pathway enrichment and cellular assays such as mitochondrial respiration and cholesterol level of PQ-treated HBMECs were performed to verify proteomics results. Proteomic experiment reported a total of 3753 quantified proteins out of which 419 were significantly modulated by paraquat exposure. Biological pathway enrichment revealed that the modified proteins are involved in pathways such as the ubiquinone metabolism, a pathway directly linked to mitochondrial complex I proteins. This study also unveiled the modulation of the cholesterol metabolism. In conclusion, most of the highly differentially expressed proteins (DEPs) in PQ-treated HBMECs were associated to the ubiquinone metabolism pathway confirming the well know mechanism of PQ inducing oxidative stress and inhibit mitochondrial complex I activity. Additionally, this study also described the cholesterol biosynthesis modulation on primary human brain endothelial cells not yet described.
2022-02-17 | PXD026975 | Pride
Project description:PURPOSE: Pulmonary fibrosis (PF) is a pathological state presenting at the progressive stage of heterogeneous interstitial lung disease (ILD). The molecular mechanisms are incompletely understood. We built a mouse model of lung fibrosis induced by paraquat. Using transcriptome analysis, we identified differentially expressed proteins (DEGs) and provided further functional analysis. METHODS: We built a mouse model of lung fibrosis through intratracheal instillation of paraquat. After instillation, mice were kept for 7 and 28 days, respectively. we performed time-series RNA sequencing (RNA-Seq) on the lung samples from paraquat treated mice and saline control. The DEGs were verified by qPCR. RESULTS: The transcriptome data found a total of 1345 of differentially expressed genes (DEGs) up-regulated and 844 DEGs down-regulated significantly in paraquat group on day 7. There were 511 DEGs up-regulated and 179 DEGs down-regulated remarkably on day 28 after PQ instillation (Fold Change ≥2 and Q value ≤0.001). We verified 6 significantly changed genes by qPCR, proving the accuracy of RNA-seq. CONCLUTION: Our transcriptomic study assigns genes for fibrogenesis and reveals their dynamic changes from lung injury to repair, providing new insights for the and development of biomarkers and treatment in fibrotic diseases.
2024-04-01 | GSE171625 | GEO
Project description:Toxicogenomics (tgx) is used as a tool to identify mechanisms and markers of necrosis in C57BL/6 mice treated by oral gavage using acetaminophen (APAP), isoniazid (INZ), and paraquat (PQ). Critical doses for tgx analysis were derived from a 25 day dose range finding study. For tgx analysis, livers of mice were collected 1 and 2 days after a single compound dose of 168.75, 225, and 300 mg/kg bw for APAP; 12.5, 25, and 50 mg/kg bw for PQ; and 22, 44, and 88 mg/kg bw for INZ. All samples were diluted in water.
2014-12-16 | GSE51969 | GEO
Project description:We report RNA-sequencing from ventral mid brain and striatum from paraquat, pyridaben and paraquat+maneb mice models of Parkinson's disease. We observed several differentially expressed genes upon pesticide exposure which we analyzed by pathway analysis.
2012-09-04 | GSE36232 | GEO
Project description:Since the last decade, the field of extracellular vesicles (EVs) has increasingly grown. These “intracellular messengers” became interesting as biomarker source in the SNC research, because of their content, which may reflect the physiological state of their donor cells in a context of an external stimuli. However, still little is known about EVs released from cell types constituting the blood-brain barrier (BBB), especially on the human brain microvascular endothelial cells (HBMECs). The current study aimed to isolate and characterize EVs from HBMECs and to analyze the EVs proteome modulation after an external stimulate such as the Paraquat (PQ), a neurotoxicant. Size distribution, quantity and presence of EV markers were assessed. Identification and quantification of EVs proteins was conducted by data-independent acquisition mass-spectrometry (DIA-MS). Signature pathway of PQ-treated EVs were analyzed by gene ontology terms and pathway enrichment. Results present evidence that PQ-treated HBMECs and EVs are sharing proteins belonging to the ubiquinone metabolism and to the transcription HIF-1 targets pathways with a highly significant p-values, suggesting that those pathways may be a potential EVs signature of the PQ-induced toxicity in the BBB.
2021-09-10 | PXD024691 | Pride