Zinc is a common metal in most ambient particulate matter (PM), and has been proposed to be a causative component in PM-induced adverse cardiovascular health effects. Zinc is also an essential metal and has the potential to induce many physiological and nonphysiological changes. Most toxicological studies employ high levels of zinc. We hypothesized that subchronic inhalation of environmentally relevant levels of zinc would cause cardiac changes in healthy rats. To address this question, healthy male WKY rats (12 wks age) were exposed via nose only inhalation to filtered air or 10, 30 or 100 ug/m3 of aerosolized Zn in sulfate form, 5 h/d, 3 d/wk for 16 wks. Necropsies occurred 48 h after the last exposure to ensure effects were due to chronic exposure rather than the last exposure. No significant changes were observed in neutrophil or macrophage count, total lavageable cells, or enzyme activity levels (lactate dehydrogenase, n-acetyl ?-D-glucosaminidase, ?-glutamyl transferase) in bronchoalveolar lavage fluid, indicating minimal pulmonary effect. In the heart, cytosolic glutathione peroxidase activity decreased, while mitochondrial ferritin levels increased and succinate dehydrogenase activity decreased, suggesting a mitochondria-specific effect. Although no cardiac pathology was seen, cardiac gene array analysis indicated changes in genes involved in cell signaling, a pattern concordant with known zinc effects. These data indicate that inhalation of zinc at environmentally relevant levels may induce cardiac effects. While changes are small in healthy rats, these may be especially relevant in individuals with pre-existent cardiovascular disease.
Subchronic inhalation of zinc sulfate induces cardiac changes in healthy rats.
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View SamplesDEP 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.)
One-month diesel exhaust inhalation produces hypertensive gene expression pattern in healthy rats.
Specimen part
View SamplesZinc (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.
The role of particulate matter-associated zinc in cardiac injury in rats.
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View SamplesTo search for rapid changes in gene expression following BCR activation, we performed DNA microarray analysis of activated splenic B cells with and without anti-IgM treatment for 3 hour. The expression of a remarkably large set of genes differed significantly.
Initiation of antigen receptor-dependent differentiation into plasma cells by calmodulin inhibition of E2A.
Age, Specimen part
View SamplesEnteric glial cells (EGCs) are the main constituent of the enteric nervous system and share similarities with astrocytes from the central nervous system including their reactivity to an inflammator microenvironment. In this study we isolated GFAP-positive myenteric glia from FVB/hGFAP-eGFP transgenic postnatal day 7 mice. Following cell sorting for the eGFP reporter, GFAP-positive EGCs were cultured for 3 weeks to generate neurosphere-like bodies. This cell culture was stimulated with LPS for 48 h and cells were employed for gene expression profiling. LPS-stimulated cell cultures were compared to untreated control cell cultures. Enriched GFAP+ EGC cultures secreted increased levels of prominent inflammatory cytokines upon LPS stimulation. Further, in vitro cultures were compared to GFAP-eGFP-positive cells directly analyzed after cell sorting of small intestinal LMMP digests (in vivo) to assess alterations in transcriptomic profiles due to the in vitro culture.
Activation of Myenteric Glia during Acute Inflammation In Vitro and In Vivo.
Specimen part
View SamplesPhloem-feeding pests cause extensive crop damage throughout the world yet little is understood about how plants perceive and defend themselves from these threats. The silverleaf whitefly (SLWF; Bemisia tabaci type B) is a good model for studying phloem-feeding insect-plant interactions as SLWF nymphs cause little wounding and have a long, continuous interaction with the plant. Using the Arabidopsis ATH1 GeneChip, the global responses to Silverleaf Whitefly 2nd instar feeding were examined.
Arabidopsis transcriptome changes in response to phloem-feeding silverleaf whitefly nymphs. Similarities and distinctions in responses to aphids.
Age
View SamplesTranscriptome analysis was performed to determine what gene expression changes occur in response to treatment of the plant-derived compound harmine and to determine its effect on protein kinase C agonist reactivation of latent HIV.
Harmine enhances the activity of the HIV-1 latency-reversing agents ingenol A and SAHA.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
Integrated analysis of global mRNA and protein expression data in HEK293 cells overexpressing PRL-1.
Cell line
View SamplesIdiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix proteins deposition. Epstein - Barr virus (EBV) has previously been localised to alveolar epithelial cells of IPF patients. In this study we utilised a microarray based differential gene expression analysis strategy to identify potential molecular drivers of EBV associated lung fibrosis. We employed an alveolar epithelial cell line infected with EBV (A-Akata). Lytic phase infection induced in the A-Akata cells by TPA/BA treatment resulted in increase of TGFbeta1 and TIEG1 mRNA expression. Treatment of the A-Akata cells with ganciclovir,
Alveolar epithelial cell injury with Epstein-Barr virus upregulates TGFbeta1 expression.
No sample metadata fields
View SamplesThe multifunctional protein tyrosine phosphatase PRL-1 (Gene Symbol: PTP4A1) has been identified as an important oncogene with roles in promoting cell proliferation, survival, migration, invasion, and metastasis. However, little is currently known about the signaling pathways through which it mediates its effects.
Integrated analysis of global mRNA and protein expression data in HEK293 cells overexpressing PRL-1.
Cell line
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