Effect of pm2.5 maternal exposure on DNA methylation in the offspring myocardium
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE229560 | GEO | 2025/04/01
REPOSITORIES: GEO
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Project description:Open tenotomy of the Achilles tendon of 6 rats was performed. The animals were divided into two groups according to exposure of PM2.5 (particulate matter less than 2.5 µm): control group (Non-PM group) or PM exposure group (PM group). After 6 weeks of PM exposure, the tendon RNA was extracted and anlyzed.
2022-08-03 | GSE200463 | GEO
Project description:Open tenotomy of the Achilles tendon of 6 rats was performed. The animals were divided into two groups according to exposure of PM2.5 (particulate matter less than 2.5 µm): control group (Non-PM group) or PM exposure group (PM group). After 6 weeks of PM exposure, the tendon DNA was extracted and anlyzed. Genome-wide DNA methylation profiles were determinen. DNA amplicons were prepared using Differential Methylation Hybridization (DMH) method, subsequently hybridized on to the Customized Agilent Rat CpG island Microarray. The goal was to unravel the DNA methylation patterns in different subgropus of tendon tissue according to partciulate matter exposure.
2022-08-03 | GSE200709 | GEO
Project description:Exposure to particulate matter (PM) is consistently associated with increased morbidity and mortality attributable in part to respiratory illnesses. The alveolar macrophage (AM) is one of the cell types in the lung constantly exposed to and activated by ambient pollutants. Upon contact with environmental particulate pollutants, AM produces reactive oxygen species (ROS) and antioxidant enzymes, but the scope of this oxidative stress response induced by PM remains poorly defined. In this study, we used microarray analysis to determine the gene expression profile in human alveolar macrophages upon exposure to PM and sought to gain more insight into the global response of pro- and anti-oxidant enzymes to PM exposure. Human AM were obtained by bronchoscopy from normal individuals. They were then incubated with Chapel Hill PM2.5 (1 ug/ml) or vehicle for 4 hours (n = 6 independent samples each). mRNAs were extracted, amplified and hybridized to Agilent Human 1A microarray. Differentially expressed genes were identified by Statistical Analysis for Microarrays (SAM) with a FDR of 10% and a P ≤ 0.05. Significant genes were also mapped with Gene Ontology (GO) based on their molecular function. We found 34 and 41 up- and down-regulated genes respectively. Of these, 22 genes (~30%) were involved in metal binding and 14 genes were linked to oxidative stress, including 5 metallothionein-1 (MT1) isoform genes. In lung cells, addition of MT-1F in the medium attenuated PM2.5-induced H2O2 production while knockdown of MT1F gene expression increased H2O2 and IL-6 release induced by PM2.5. Our microarray experiments provided a global view of gene expression after in vitro PM2.5 exposure in human AM. The expression profile was most notable for differential expression of genes related to metal binding and oxidative stress, especially upregulation of MT1 isoform genes. Our findings suggest that metals associated with PM, e.g., zinc, copper, and arsenic, induce MT-1 and may be the primary mediators for PM-induced oxidative stress. Keywords: in vitro exposure, PM2.5 particle treatment, human alveolar macrophages
2008-05-01 | GSE10394 | GEO
Project description:Background Airborne fine particulate matter with diameter < 2.5 μm (PM2.5), can reach the alveolar regions of the lungs, and is associated with over 4 million premature deaths per year worldwide. However, the source-specific consequences of PM2.5 exposure remain poorly understood. A major, but unregulated source is car brake wear, which exhaust emission reduction measures have not diminished.AQ1 Methods We used an interdisciplinary approach to investigate the consequences of brake-wear PM2.5 exposure upon lung alveolar cellular homeostasis using diesel exhaust PM as a comparator. This involved RNA-Seq to analyse global transcriptomic changes, metabolic analyses to investigate glycolytic reprogramming, mass spectrometry to determine PM composition, and reporter assays to provide mechanistic insight into differential effects. Results We identified brake- wear PM from copper-enriched non-asbestos organic, and ceramic brake pads as inducing the greatest oxidative stress, inflammation, and pseudohypoxic HIF activation (a pathway implicated in diseases associated with air pollution exposure, including cancer, and pulmonary fibrosis), as well as perturbation of metabolism, and metal homeostasis compared with brake wear PM from low- or semi-metallic pads, and also, importantly, diesel exhaust PM. Compositional and metal chelator analyses identified that differential effects were driven by copper. Conclusions We demonstrate here that brake-wear PM may perturb cellular homeostasis more than diesel exhaust PM. Our findings demonstrate the potential differences in effects, not only for non-exhaust vs exhaust PM, but also amongst different sources of non-exhaust PM. This has implications for our understanding of the potential health effects of road vehicle-associated PM. More broadly, our findings illustrate the importance of PM composition on potential health effects, highlighting the need for targeted legislation to protect public health.
2025-02-13 | GSE286058 | GEO
Project description:Bronchial epithelial cells, which line the airway of the respiratory tract, undergo genome-wide level changes in gene expression and DNA methylation particularly when exposed to fine (< 2.5 µm) PM (PM2.5). Although some of these changes have been reported in other studies, a comparison of how different doses and duration of exposure affect both the gene transcriptome and DNA methylome has not been done. We exposed BEAS-2B, a bronchial epithelial cell line, to a single exposure of high (30 µg/cm2) or low (1 µg/cm2) dose of PM2.5 (obtained from Beijing, China in 2015) for 24 hours. We also exposed BEAS-2B cells to repeated exposures of low dose (1 µg/cm2) PM2.5 every day for seven days. We then examined the transcriptomic changes (by RNA-Seq) and DNA methylomic changes (by enhanced reduced representation bisulfite sequencing). Widespread changes in gene expression occurred after cells were exposed to a single, high dose (30 µg/cm2) exposure of PM2.5 for 24 h. These genes were enriched in pathways regulating MAPK signaling, PI3K-Akt signaling, cytokine interactions, IL6, and P53. DNA methylomic analysis showed that nearly half of the differentially expressed genes were found to also have DNA methylation changes. Cells exposed to a lower dose (1 µg/cm2) of PM2.5 demonstrated a similar, but more attenuated change in gene expression. Cells exposed to repeated doses of PM2.5 for seven days, however, demonstrated a different set of genes that were differentially expressed compared to a single exposure. The DNA methylation changes that occurred with repeated, low dose exposure were also different from single high dose exposures and skewed towards overall hypomethylation. This hypomethylation corresponded with an increase in expression of ten-eleven translocation enzymes. Overall, these data demonstrate how variations in dose and duration of PM2.5 exposure induce distinct differences in the transcriptomic and DNA methylomic profile of bronchial epithelial cells.
2020-12-21 | GSE155616 | GEO
Project description:Bronchial epithelial cells, which line the airway of the respiratory tract, undergo genome-wide level changes in gene expression and DNA methylation particularly when exposed to fine (< 2.5 µm) PM (PM2.5). Although some of these changes have been reported in other studies, a comparison of how different doses and duration of exposure affect both the gene transcriptome and DNA methylome has not been done. We exposed BEAS-2B, a bronchial epithelial cell line, to a single exposure of high (30 µg/cm2) or low (1 µg/cm2) dose of PM2.5 (obtained from Beijing, China in 2015) for 24 hours. We also exposed BEAS-2B cells to repeated exposures of low dose (1 µg/cm2) PM2.5 every day for seven days. We then examined the transcriptomic changes (by RNA-Seq) and DNA methylomic changes (by enhanced reduced representation bisulfite sequencing). Widespread changes in gene expression occurred after cells were exposed to a single, high dose (30 µg/cm2) exposure of PM2.5 for 24 h. These genes were enriched in pathways regulating MAPK signaling, PI3K-Akt signaling, cytokine interactions, IL6, and P53. DNA methylomic analysis showed that nearly half of the differentially expressed genes were found to also have DNA methylation changes. Cells exposed to a lower dose (1 µg/cm2) of PM2.5 demonstrated a similar, but more attenuated change in gene expression. Cells exposed to repeated doses of PM2.5 for seven days, however, demonstrated a different set of genes that were differentially expressed compared to a single exposure. The DNA methylation changes that occurred with repeated, low dose exposure were also different from single high dose exposures and skewed towards overall hypomethylation. This hypomethylation corresponded with an increase in expression of ten-eleven translocation enzymes. Overall, these data demonstrate how variations in dose and duration of PM2.5 exposure induce distinct differences in the transcriptomic and DNA methylomic profile of bronchial epithelial cells.
2020-12-21 | GSE155615 | GEO
Project description:Chronic exposure to ambient particulate matter (PM) increases the risk of cardiovascular disease (CVD). One proposed mechanism linking PM exposure and CVD is the induction of low-grade systemic inflammation that underlies disease progression. However, the intermediaries that relay signals from the proximal sites of inflammation to the periphery remain unknown. We have previously shown that fine PM (PM2.5) alter red blood cell distribution width. Therefore, the overall goal of this study was to elucidate how PM exposure impacts the spleen and splenic macrophages which are primarily responsible for the turnover of aged and damaged red blood cells.
2024-12-02 | GSE262906 | GEO
Project description:Exposure to particulate matter (PM) is consistently associated with increased morbidity and mortality attributable in part to respiratory illnesses. The alveolar macrophage (AM) is one of the cell types in the lung constantly exposed to and activated by ambient pollutants. Upon contact with environmental particulate pollutants, AM produces reactive oxygen species (ROS) and antioxidant enzymes, but the scope of this oxidative stress response induced by PM remains poorly defined. In this study, we used microarray analysis to determine the gene expression profile in human alveolar macrophages upon exposure to PM and sought to gain more insight into the global response of pro- and anti-oxidant enzymes to PM exposure. Human AM were obtained by bronchoscopy from normal individuals. They were then incubated with Chapel Hill PM2.5 (1 ïg/ml) or vehicle for 4 hours (n = 6 independent samples each). mRNAs were extracted, amplified and hybridized to Agilent Human 1A microarray. Differentially expressed genes were identified by Statistical Analysis for Microarrays (SAM) with a FDR of 10% and a P ⤠0.05. Significant genes were also mapped with Gene Ontology (GO) based on their molecular function. We found 34 and 41 up- and down-regulated genes respectively. Of these, 22 genes (~30%) were involved in metal binding and 14 genes were linked to oxidative stress, including 5 metallothionein-1 (MT1) isoform genes. In lung cells, addition of MT-1F in the medium attenuated PM2.5-induced H2O2 production while knockdown of MT1F gene expression increased H2O2 and IL-6 release induced by PM2.5. Our microarray experiments provided a global view of gene expression after in vitro PM2.5 exposure in human AM. The expression profile was most notable for differential expression of genes related to metal binding and oxidative stress, especially upregulation of MT1 isoform genes. Our findings suggest that metals associated with PM, e.g., zinc, copper, and arsenic, induce MT-1 and may be the primary mediators for PM-induced oxidative stress. Keywords: in vitro exposure, PM2.5 particle treatment, human alveolar macrophages Total RNA was isolated from alveolar macrophages from 6 subjects were treated in vitro with PM2.5 particles or vehicle control for 4 hrs. All particle-treated samples were co-hybridized with the common reference sample (pool of all 6 vehicle-treated samples) twice with Cy3 and Cy5 dyes flipped (12 hybridizations). Three samples were also co-hybridized with its own individual control (vehicle-treatment for the same subject) with Cy3 and Cy5 dyes flipped (6 additional hybridizations).
2008-05-01 | E-GEOD-10394 | biostudies-arrayexpress
Project description:Epidemiological studies have demonstrated that exposure to particulate matter (PM) ambient pollution has adverse effects on lung health, exacerbated by cigarette smoking. Fine airborne particles <2.5 µm (PM2.5) are the most harmful of the urban pollutants, and the most closely linked to respiratory disease. Based on the knowledge that the small airway epithelium (SAE) plays a central role in pathogenesis of smoking-related lung disease, we hypothesized that elevated PM2.5 levels are associated with dysregulation of SAE gene expression.
2018-06-19 | GSE108134 | GEO
Project description:Zinc (Zn) is a major elemental component of respirable ambient particulate matter (PM) detected often at alarming levels in urban air. Exposure to PM has been widely associated with increased cardiovascular morbidity and mortality, however, it is not known what components or sources of PM are causative. We recently demonstrated that long-term episodic inhalation of combustion PM, having similar amount of Zn found in urban PM, caused myocardial lesions in rats. We further demonstrated that a single pulmonary exposure to Zn at high concentration is associated with disturbances in cardiac mitochondrial function, ion channel regulation, calcium homeostasis, and cell signaling. Therefore, in this study we investigated the role of PM-associated Zn in cardiac injury using multiple exposure scenarios. Male Wistar-Kyoto (WKY) rats of 12-14 wks age were intratracheally exposed (once per wk x 8 or16 wks) to either (1) saline (control); (2) PM having no soluble Zn; (3) combustion PM suspension containing 14.5 ug/mg water-soluble Zn at high and (4) low dose levels, (5) the aqueous fraction of this suspension devoid of solid insoluble particulate fraction (14.5 ug/mg soluble Zn), or (6) Zn sulfate. Zn concentrations were identical in groups 3, 5 and 6. Pulmonary toxicity was apparent in all exposure groups when compared to saline as determined by recovery of cells in bronchoalveolar lavage fluid. Long-term exposure to PM with or without soluble Zn, or Zn sulfate caused distinct myocardial lesions characterized by subepicardial and randomly distributed myocardial inflammation, degeneration, and fibrosis. The lesion severity was higher in those groups receiving Zn PM. Because cardiac mitochondria are likely the primary target of inhaled metal or other absorbed PM components, we analyzed mitochondrial DNA damage using QPCR and found that all exposure groups except those exposed to PM without Zn caused variable degree of damage. Aconitase activity, sensitive to inhibition by oxidative stress was inhibited slightly but significantly in rats receiving zinc sulfate. Although modest, microarray (Affymetrix) analysis revealed expression changes in the heart reflective of effects on cell signaling, inflammation/oxidative stress, mitochondrial fatty acid metabolisms and cell cycle regulation in rats exposed to zinc sulfate. However, these changes were minimal following exposure to PM devoid of soluble metals. We demonstrate that episodic subchronic pulmonary exposure to zinc sulfate causes cardiac injury and mitochondrial DNA damage. Thus, water-soluble PM-associated zinc may be one of the PM components responsible for cardiovascular morbidity. Experiment Overall Design: Group 1 received Saline to serve as a control. Group 2 received Mount St. Helenâs ash, which does not contain any water-soluble zinc or other metals such that we can delineate any cardiac effect secondary to pulmonary deposition of these particles as these fine mode particles themselves are not likely to translocate to the heart. Group 3 received whole saline suspension of the same fugitive oil combustion particle sample used in the previous study, which contained insoluble components plus water-soluble zinc (Kodavanti et al., 2003; 14.5 ug/mg zinc) and also a small amount of water-soluble nickel (3.0 µg/mg). Elemental composition of this PM is comparable to Ottawa urban PM (Kodavanti et al., 2003). Group 4 also received same particle sample but at half the dose than group 3. Group 5 received saline-soluble or leachable fraction of PM-HD devoid of any solid material but contained soluble components including zinc and nickel. And, group 6 received zinc sulfate at concentration that was present in groups 3 or 5. This design allowed us to test if cardiac injury in rats was due to leached of zinc or solid particles. There were 4 replicates per treatment group.
2008-06-14 | E-GEOD-6541 | biostudies-arrayexpress