run_metadata: 52362
This data as json
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 52362 | SRR9182368 | SRX5954846 | SRS4865338 | SRP200180 | PRJNA545942 | Targeting redox metabolism: the perfect storm induced by acrylamide poisoning in the brain | PRJNA545942 | Other | Acrylamide is a recognized carcinogen that has strong neurotoxic effectseffects in humans and in experimental animals although the molecular mechanisms underlying these neurotoxic effects are not completely understood. We studied acrylamide neurotoxicity in adult zebrafish using an integrated approach that included biochemical transcriptomic proteomic and metabolomic data. Brain samples from exposed and control zebrafish were subjected to proton NMR for metabolomic analysis to MALDI TOF mass spectrometry for proteome analysis and to high throughput RNA sequencing for transcriptomic analysis. We detected the formation of acrylamide adducts with thiol groups in the brain metabolome and the accumulation of acrylamide conjugates and propionamide adducts in Cys residues of proteins. These combined effects resulted in a quasi complete depletion of glutathione and to the inactivation of different components of the thioredoxin system. Multi omic functional analyses identified microtubules thioredoxin related proteins transmembrane transport redox metabolism and catalytic activity as the cellular functions significantly altered by acrylamide in the fish brain. We propose that the combined loss of function of both redox metabolism related systems configure a perfect storm that explains many acrylamide neurotoxic effects like the dysregulation of genes related to microtubules presynaptic vesicle alteration and behavioral alterations. We further propose an Adverse Outcome Pathway of acrylamide neurotoxicity connecting the different toxic effects across different levels of organization from molecular interactions to behavioral changes. Our mechanistical approach may help developing new treatments against the neurotoxic effects of acrylamideand of other neurotoxicants that may share its toxic mode of action. | ZF Brain Control NV 3 | NV 3 | strain:WT|dev stage:Adult|sex:male|tissue:Brain|treatment:Control replicate 3|BioSampleModel:Model organism or animal | RNA seq of Danio rerio: control adult male brain | NV 3 | NV 3 | Zebrafish brain RNA was sent to the Vanderbilt Technologies for Advanced Genomics Vanderbilt University Nashville TN for library preparation and sequencing on the Illumina Novaseq platform | RNA-Seq | TRANSCRIPTOMIC | RANDOM PCR | PAIRED | ILLUMINA | Illumina NovaSeq 6000 | SRP200180 | 2465-NV-3-TCGGATTC-CGCAACTA_S351_R1_001.fastq.gz 2465-NV-3-TCGGATTC-CGCAACTA_S351_R2_001.fastq.gz | fastq fastq | 12058574400.0 | 40195248.0 | 2465 NV 3 TCGGATTC CGCAACTA S351 R1 001.fastq.gz | 0:150 1:150 | A:3459397409;C:2538226914;G:2686587266;T:3357533701;N:16829110 | 150 | 150 | 3459397409 | 2538226914 | 2686587266 | 3357533701 | 16829110 | SRX5954846 | SRS4865338 | SRA893242 | Mississippi State University|Institute for Genomics, Biocomputing & Biotechnolo | Mississippi State University | 2 | 0.91597 | 0.90969 | 0.20272 | 0.19926 | 0.71683 | 0.71705 | 0.50712 | 0.51001 | 150 | 150 | B | B | biological fallback assumption | illumina | novaseq_era | unknown | random_priming | unknown | bulk | unknown | unknown | United States | 2019-06-03 | Adult | Adult | Brain | Nervous System |