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GSE80733
Homo sapiens
23 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
Determining mechanism-based biomarkers that distinguish adaptive and adverse cellular processes is critical to understanding the health effects of environmental exposures. Shifting from in vivo, low-throughput toxicity studies to high-throughput screening (HTS) paradigms and risk assessment based on in vitro and in silico testing requires utilizing toxicity pathway information to distinguish adverse outcomes from recoverable adaptive events. Little work has focused on oxidative stresses in human airway for the purposes of predicting adverse responses. We hypothesize that early gene expression-mediated molecular changes could be used to delineate adaptive and adverse responses to environmentally-based perturbations. Here, we examined cellular responses of the tracheobronchial airway to zinc (Zn) exposure, a model oxidant. Airway derived BEAS-2B cells exposed to 210 M Zn2+ elicited concentration- and time-dependent cytotoxicity. Normal, adaptive, and cytotoxic Zn2+ exposure conditions were determined with traditional apical endpoints, and differences in global gene expression around the tipping point of the responses were used to delineate underlying molecular mechanisms. Bioinformatic analyses of differentially expressed genes indicate early enrichment of stress signaling pathways, including those mediated by the transcription factors p53 and NRF2. After 4 h, 154 genes were differentially expressed (p <0.01) between the adaptive and cytotoxic Zn2+ concentrations. Nearly 40% of the biomarker genes were related to the p53 signaling pathway with 30 genes identified as likely direct targets using a database of p53 ChIP-seq studies. Despite similar p53 activation profiles, these data revealed widespread dampening of p53 and NRF2-related genes as early as 4 h after exposure at higher, unrecoverable Zn2+ exposures. Thus, in our model early increased activation of stress response pathways indicated a recoverable adaptive event. Overall, this study highlights the importance of characterizing molecular mechanisms around the tipping point of adverse responses to better inform HTS paradigms.
Publication Title
Developing a Gene Biomarker at the Tipping Point of Adaptive and Adverse Responses in Human Bronchial Epithelial Cells.
Sample Metadata Fields
Cell line, Time
View Samples- Staphylococcus aureus
- 27 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 24 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
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.
Publication Title
The role of particulate matter-associated zinc in cardiac injury in rats.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
DEP exposure is linked to increases in cardiovascular effects. This effect is enhanced in individuals with pre-existing disease. Animal models of cardiovascular disease are used to study this susceptibility. The heart is rich in mitochondria, which produce high levels of free radicals, leading to inactivation of tricarboxylic acid cycle enzymes. We hypothesized that a 4-wk DEP inhalation would result in strain-related structural impairment of cardiac mitochondria and changes in these enzyme activities in WKY and SHR. Male rats (12-14 wks age) were exposed whole body to air or 0.5 or 2.0 mg/m3 DEP for 6h/d, 5 d/wk for 4 wks. Neutrophilic influx was noted in the bronchoalveolar lavage fluid in both strains. A slightly lower level of baseline cardiac mitochondrial aconitase activity was seen in SHR than WKY. Aconitase activity appeared to be decreased in an exposure related manner in both strains. Significantly higher baseline levels of cardiac cytosolic ferritin and aconitase activity were seen in the SHR than WKY. No exposure-related changes were noted in either of these measures. Mitochondrial succinate and isocitrate dehydrogenase activities were not changed following DEP exposure in either strain. Transmission electron microscopy images of the heart indicated abnormalities in cardiac mitochondria of control SHR but not control WKY. No exposure related ultrastructural changes were induced by DEP in either strain. In conclusion, strain differences in cardiac biomarkers of oxidative stress and structure of mitochondria exist between SHR and WKY. DEP exposure results in small changes in cardiac mitochondrial and cytosolic markers of oxidative stress. (Abstract does not represent USEPA policy.)
Publication Title
One-month diesel exhaust inhalation produces hypertensive gene expression pattern in healthy rats.
Sample Metadata Fields
Specimen part
View Samples- Staphylococcus aureus
- 15 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
In the present study, we employed Affymetrix Staphylococcus aureus GeneChip arrays to investigate the dynamics of global gene expression profiles during the cellular response of Staphylococcus aureus to Ortho-Phenylphenol, which involved initial growth inhibition and metabolism.
Publication Title
Microarray analysis of toxicogenomic effects of ortho-phenylphenol in Staphylococcus aureus.
Sample Metadata Fields
No sample metadata fields
View Samples- Staphylococcus aureus
- 15 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
Global gene expression analysis of Staphylococcus aureus following Ortho-Benzyl-Para-Chloro Phenol (OBPCP) treatment using Affymetrix GeneChip arrays. Results from this study provide insight into the molecular mechanisms underlying the cellular response of Staphylococcus aureus to OBPCP.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Staphylococcus aureus
- 15 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
In the present study, we employed Affymetrix Staphylococcus aureus GeneChip arrays to investigate the dynamics of global gene expression profiles during the cellular response of Staphylococcus aureus to triclosan, which involved initial growth inhibition and metabolism.
Publication Title
Microarray analysis of toxicogenomic effects of triclosan on Staphylococcus aureus.
Sample Metadata Fields
No sample metadata fields
View Samples- Staphylococcus aureus
- 12 Downloadable Samples
- Affymetrix S. aureus Genome Array (saureus)
Description
Global gene expression analysis of Staphylococcus aureus following Para-Tertiary Amyl Phenol (PTAP) treatment using Affymetrix GeneChip arrays. Results from this study provide insight into the molecular mechanisms underlying the cellular response of Staphylococcus aureus to PTAP.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 12 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
In the present study, we employed Affymetrix Pseudomonas aeruginosa GeneChip arrays to investigate the dynamics of global gene expression profiles during the cellular response of Pseudomonas aeruginosa to ortho-phenylphenol, which involved initial growth inhibition and metabolism.
Publication Title
Toxicogenomic response of Pseudomonas aeruginosa to ortho-phenylphenol.
Sample Metadata Fields
No sample metadata fields
View Samples- Pseudomonas aeruginosa
- 9 Downloadable Samples
- Affymetrix Pseudomonas aeruginosa Array (paeg1a)
Description
In the present study, we employed Affymetrix Pseudomonas aeruginosa GeneChip arrays to investigate the dynamics of global gene expression profiles during the cellular response of Pseudomonas aeruginosa to Chlorhexidine diacetate, which involved initial growth inhibition and metabolism.
Publication Title
Global transcriptomic response of Pseudomonas aeruginosa to chlorhexidine diacetate.
Sample Metadata Fields
No sample metadata fields
View Samples