Formaldehyde exposure alters miRNAs expression profiles in olfactory bulb
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ABSTRACT:
ORGANISM(S): synthetic construct Mus musculus
PROVIDER: GSE59369 | GEO | 2015/08/04
SECONDARY ACCESSION(S): PRJNA255204
REPOSITORIES: GEO
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Project description:Neurotoxicity of formaldehyde (FA) in the human health attracted intensive studies Long-term exposure to FA leads to learning and memory decline and is responsible for the multiple chemical sensitivity (MCS) or sick building syndrome (SBS). It was cleared that Formaldehyde impairs Learning and Memory in Hippocampal. however ,it is unclear if FA can disturb the olfactory bulb function miRNAs alterations were related to environmental chemical exposure. It was reported that FA inhale altered miRNAs expression in the nasal Epithelium and lung cells. In the present study, FA inhalation significatly alters miRNA expression profiles within olfactory bulb Eight week ICR male mouse. Mice were randomly assigned to three groups. The FA group exposed to 3ppm FA for six hours for consecutive 1 and 7days in a chamber which was described previously. The standard group was kept in same condition except the FA. After expose, both group mice were deeply anesthetized with isoflurane and decapitated. The OB was rapidly dissected
2015-08-04 | E-GEOD-59369 | biostudies-arrayexpress
Project description:Formaldehyde (FA) is a commercially important chemical with numerous and diverse uses. In this study, a functional toxicogenomics approach was utilized in the model eukaryotic yeast Saccharomyces cerevisiae to identify genes and cellular processes modulating the cellular toxicity of FA. Our results demonstrate mutant strains deficient in multiple DNA repair pathways were sensitive to FA. The SKI complex and its associated factors, which regulate mRNA degradation by the exosome, were also required for FA tolerance..
2016-11-09 | GSE83398 | GEO
Project description:Formaldehyde (FA) is an environmental and occupational chemical carcinogen. Recent studies demonstrated that exogenous FA caused only a modest increase in DNA adducts above levels caused by endogenous FA. This raised a possibility that epigenetic mechanisms might contribute to FA-mediated carcinogenicity. Here we report a drastic decrease of acetylation of N-terminal tails of the cytosolic histones following FA exposure, the modifications important for histone nuclear import and assembly into chromatin. In fact, the amount of histone proteins in chromatin fraction decreases following FA exposure. Moreover, the histone depletions are evident at most of the genomic loci we tested, suggesting that FA compromises chromatin assembly. Notably, FA increases chromatin accessibility and changes expression of hundreds of cancer-related genes. Importantly, the knockdown of histone H3.3 (a H3 variant), which mimics inhibition of chromatin assembly, facilitates FA-mediated cell transformation. We propose that inhibiting chromatin assembly represents a novel mechanism for FA carcinogenesis.
2017-10-16 | GSE87541 | GEO
Project description:Formaldehyde (FA), an endogenous cellular aldehyde, is a rat nasal carcinogen. In this study, concentration- and exposure-duration transitions in FA mode of action (MOA) were examined with pharmacokinetic (PK) modeling for tissue formaldehyde acetal (FAcetal) and glutathione (GSH) and with histopathology and gene expression studies for tissue responses in nasal epithelium from rats exposed to 0, 0.7, 2, 6, 10 or 15 ppm FA 6 hr/day for 1, 4 or 13 weeks. The study had two goals. The first goal was to develop a basic PK model to estimate various forms of tissue formaldehyde and tissue glutathione (GSH). The second goal was to compare histopathology and gene expression changes in nasal tissues caused by inhalation of FA with changes in tissue FAcetal and free GSH calculated from the PK model. Patterns of gene expression varied with concentration and with duration. At 0.7 and 2 ppm, sensitive response genes (SRGs) - associated with cellular stress, thiol transport/reduction, inflammation, and cell proliferation - were similarly upregulated at all exposure durations. At 6 ppm and greater, gene expression changes showed enrichment of pathways involved in cell cycle, DNA repair, and apoptosis processes. ERBB, EGFR, WNT, TGF-β, Hedgehog, and Notch signaling were also enriched in differentially expressed genes. Benchmark doses (BMDs) for genes in significantly enriched pathways were lower at 13 weeks than at 1 or 4-week. The transcriptional and histological changes corresponded to PK model-predicted changes in free GSH at 0.7 and 2 ppm and in FAcetal at 6 ppm. DNA-replication stress, enhanced proliferation, metaplasia, and stem cell-niche activation appear to be associated with FA carcinogenesis at 6 ppm and above. Dose dependencies in MOA, the presence of high physiological FAcetal, and non-linear FAcetal/GSH tissue kinetics indicate that FA concentrations below 150 ppb (and probably any concentrations below irritant levels, i.e., ~ 1 ppm) would not increase cancer risks of inhaled FA in the nose or any other tissue. Closer examination of dose response relationships for endogenous compound toxicity could help guide biologically relevant approaches for chemical risk assessment.
2010-07-28 | GSE23179 | GEO
Project description:One-carbon metabolism is a universal hub for cellular metabolism and epigenetic regulation.1–3 Here, we report that formaldehyde (FA), a one-carbon unit that organisms produce in substantial quantities through folate metabolism,4 is a regulator of the one-carbon cycle via the biosynthesis of S-adenosyl-L-methionine (SAM), an essential one-carbon building block for synthesis of nucleotides, amino acids, and methylated nucleic acids and proteins.5 Activity-based protein profiling (ABPP) in mouse liver tissue identifies FA-sensitive cysteine sites across the proteome, revealing several one-carbon cycle targets including S-adenosylmethionine synthetase isoform 1 (MAT1A), the terminal enzyme in SAM biosynthesis. Biochemical studies of the formaldehyde-MAT1A interaction establish FA-dependent inhibition of MAT1A activity through a conserved C120 site, as the MAT2A isoform lacking this cysteine is not FA-sensitive. CRISPR knockout-generated HepG2 cell models that predominantly express either MAT1A or MAT2A show that MAT1A-positive cells respond to FA treatment in a dose-dependent manner by decreasing their SAM levels and downstream RNA methylation, whereas the MAT2A-positive cells are not affected by FA. Our findings reveal an unexpected interplay between SAM and FA, two central one-carbon units to influence the overall methylation potential of the cell.
2023-11-02 | PXD018251 | Pride
Project description:Formaldehyde (FA), an endogenous cellular aldehyde, is a rat nasal carcinogen. In this study, concentration- and exposure-duration transitions in FA mode of action (MOA) were examined with pharmacokinetic (PK) modeling for tissue formaldehyde acetal (FAcetal) and glutathione (GSH) and with histopathology and gene expression studies for tissue responses in nasal epithelium from rats exposed to 0, 0.7, 2, 6, 10 or 15 ppm FA 6 hr/day for 1, 4 or 13 weeks. The study had two goals. The first goal was to develop a basic PK model to estimate various forms of tissue formaldehyde and tissue glutathione (GSH). The second goal was to compare histopathology and gene expression changes in nasal tissues caused by inhalation of FA with changes in tissue FAcetal and free GSH calculated from the PK model. Patterns of gene expression varied with concentration and with duration. At 0.7 and 2 ppm, sensitive response genes (SRGs) - associated with cellular stress, thiol transport/reduction, inflammation, and cell proliferation - were similarly upregulated at all exposure durations. At 6 ppm and greater, gene expression changes showed enrichment of pathways involved in cell cycle, DNA repair, and apoptosis processes. ERBB, EGFR, WNT, TGF-β, Hedgehog, and Notch signaling were also enriched in differentially expressed genes. Benchmark doses (BMDs) for genes in significantly enriched pathways were lower at 13 weeks than at 1 or 4-week. The transcriptional and histological changes corresponded to PK model-predicted changes in free GSH at 0.7 and 2 ppm and in FAcetal at 6 ppm. DNA-replication stress, enhanced proliferation, metaplasia, and stem cell-niche activation appear to be associated with FA carcinogenesis at 6 ppm and above. Dose dependencies in MOA, the presence of high physiological FAcetal, and non-linear FAcetal/GSH tissue kinetics indicate that FA concentrations below 150 ppb (and probably any concentrations below irritant levels, i.e., ~ 1 ppm) would not increase cancer risks of inhaled FA in the nose or any other tissue. Closer examination of dose response relationships for endogenous compound toxicity could help guide biologically relevant approaches for chemical risk assessment. Eight week old male F344/CrlBR rats were exposed to formaldehyde through whole body inhalation. Whole-body exposures were performed at doses of 0, 0.7, 2, 6, 10, and 15 ppm (6 hours per day, 5 days per week). Inhalation animals were sacrified at 1, 4, and 13 weeks following initiation of exposure. Following sacrifice, tissue from the Level II region of the nose was dissected and digested with a mixture of proteases to remove the epithelial cells. The epithelial cells acquired from this section of the nose consisted primarily of transitional epithelium with some respiratory epithelium. Gene expression microarray analysis was performed on the epithelial cells.
2010-07-28 | E-GEOD-23179 | biostudies-arrayexpress
Project description:Formaldehyde exposure alters miRNAs expression profiles in olfactory bulb
| PRJNA255204 | ENA
Project description:Specific genes or encoded proteins are involved in regulating various learning models of different species through certain signaling pathways，but whether there are also regulatory genes during bimodal learning and memory is largely unknown. Using a multi-omics approach to examine gene expression changes in bees brain performed with three different learning assays, a general up-regulation of genes and proteins were observed in bimodal learning compared to controls. Protein-protein network predictions of differential proteins together with FISH assays suggest ALDH7A1 may be involved in regulation of bimodal learning and memory. Injecting siRNA-ALDH7A1 to the bee brain results in significant inhibition the expressions of ALDH7A1 and regucalcin, and increase β-alanine content. Interestingly, we found that loss of ALDH7A1 only affect visual-olfactory bimodal learning and memory, but not single visual or olfactory conditioned learning after ALDH7A1-RNAi in bees. Therefore, our data suggests that ALDH7A1 may affect bimodal learning and memory though controlling β-alanine related plasticity mechanisms.
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Project description:Abstract of associated menuscript; Quinones and alpha,beta-unsaturated carbonyls are naturally occurring electrophiles that target cysteine residues via thiol-(S)-alkylation. We analyzed the global expression profile of Bacillus subtilis to the toxic carbonyls methylglyoxal (MG) and formaldehyde (FA). Both carbonyl compounds cause a stress response characteristic for thiol-reactive electrophiles as revealed by the induction of the Spx, CtsR, CymR, PerR, ArsR, CzrA, CsoR and SigmaD regulons. MG and FA triggered also a SOS response which indicates DNA damage. Protection against FA is mediated by both the hxlAB operon, encoding the ribulose monophosphate pathway for FA fixation, and a thiol-dependent formaldehyde dehydrogenase (AdhA) and DJ-1/PfpI-family cysteine proteinase (YraA). The adhA-yraA operon and the yraC gene, encoding gamma-carboxymuconolactone decarboxylase, are positively regulated by the MerR-family regulator, YraB(AdhR). AdhR binds specifically to its target promoters which contain a 7-4-7 inverted repeat (CTTAAAG-N4-CTTTAAG) between the -35 and -10 elements. Activation of adhA-yraA transcription by AdhR requires the conserved Cys52 residue in vivo. We speculate that AdhR is redox-regulated via thiol-(S)-alkylation by aldehydes and that AdhA and YraA are specifically involved in reduction of aldehydes and degradation or repair of damaged thiol-containing proteins, respectively.
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Project description:Formaldehyde (FA) is a simple biological aldehyde that is produced inside cells and its accumulation is known to be cytotoxic. We choose to use primary human fibroblasts cells in culture (foreskin, FSK) as a physiological model to gain insight into whether an increase in the level of FA might affect cellular physiology, especially with regard to the mitochondrial compartment. Gene expression assessment by microarray analysis revealed FA affected FSK cells by altering expression of many genes including genes involved in mitochondrial function and electron transport. We were surprised to observe increased DNA double-strand breaks (DSBs) in mitochondria after exposure to FA, as revealed by accumulation of γH2A.X and 53BP1 at mitochondrial DNA foci. This was associated with mitochondrial structural rearrangements, loss of mitochondrial membrane potential and activation of mitophagy. Collectively, these results indicate that an increase in the cellular level of FA can trigger mitochondrial DNA double-strand breaks and dysfunction.
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