Endothelial cells and exposure to enviromental tobacco
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE2090 | GEO | 2005/01/20
SECONDARY ACCESSION(S): PRJNA91783
REPOSITORIES: GEO
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Project description:Endothelial cells from mice exposed to enviromental tobacco smoke for 1 or 6 weeks.
2010-06-10 | E-GEOD-2090 | biostudies-arrayexpress
Project description:Previous studies have shown that smoking induces oxidative stress and inflammation, known factors that coincide with the development and progression of lung toxicity in response to crystalline silica exposure. Nevertheless, the precise role of tobacco smoke exposure on the lung response to tobacco smoke exposure and the underlying mechanisms remain largely elusive. Therefore, the objective of the present study was to determine the effect of smoking, if any, on silica-induced pulmonary toxicity and the underlying molecular mechanisms. Pulmonary toxicity and lung gene expression profiles were determined in rats exposed to air, crystalline silica, tobacco smoke, or crystalline silica plus tobacco smoke. Silica exposure resulted in significant pulmonary toxicity which was further exacerbated by tobacco smoke exposure in the rats. Significant differences in the gene expression profiles were detected in the lungs of the rats exposed to tobacco smoke, silica or a combination of both compared with the air exposed control rats.
2024-12-31 | GSE149286 | GEO
Project description:Tobacco is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, the molecular mechanisms resulting in malignancy upon tobacco exposure are yet to be fully elucidated. We therefore sought to compare the molecular alterations in oral keratinocytes exposed to smoke and chewing tobacco. OKF6/TERT1 cells were exposed to cigarette smoke condensate or chewing tobacco for progressively increasing durations (2, 4, 6 and 8 months). We employed a TMT-based quantitative proteomics approach to investigate the adverse effects of chronic cigarette smoke or chewing tobacco exposure in oral keratinocytes. LC/MS3 analysis resulted in the quantification of 5,342 proteins and 2,821 proteins in cigarette smoke and chewing tobacco exposed cells, respectively. Upstream regulator analysis indicates the involvement of distinct regulators in CSC exposed cells compared to STE exposed cells. In addition, exome sequencing revealed discrete genetic alterations in cells exposed to each insult. Current analysis defines a clear distinction in the molecular dysregulation in oral cells in response to different tobacco-based insults. Some of the proteins dysregulated in cigarette smoke or chewing tobacco exposed cells may serve as potential early detection biomarkers which could aid in stratification of patients based on tobacco usage history.
2019-11-08 | PXD007127 | Pride
Project description:Our previous studies have shown that tobacco smoke exposure exacerbated the lung response to crystalline silica exposure in rats. The objective of the present study, a follow-up to our previous study, was to determine the effect of tobacco smoke exposure cessation on the lung response to crystalline silica exposure in the rats. Rats were exposed to air, crystalline silica (1 week followed by a 1 year progression/recovery period with no exposure), tobacco smoke (6 months of exposure followed by 6 months of recovery with no exposure), or crystalline silica (1 week) plus tobacco smoke (6 months of exposure followed by 6 months of recovery with no exposure). Lung toxicity was determined at the end of the 1-year progression/recovery period in all 4 groups of the rats. Silica exposure resulted in significant lung toxicity which was further exacerbated by tobacco smoke exposure in the rats. Cessation of cigarette smoke exposure did not result in reversal of the silica-induced lung toxicity despite exacerbation of the toxicity by tobacco smoke.
2024-12-31 | GSE155924 | GEO
Project description:To clarify how smoking leads to heart attacks and stroke, we developed an endothelial cell model (iECs) generated from human induced Pluripotent Stem Cells (iPSC) and evaluated its responses to tobacco smoke. These iECs exhibited a uniform endothelial morphology, expressed markers PECAM1/CD31, VWF/von Willebrand Factor, and CDH5/VE-Cadherin, and exhibited tube formation and Acetyl-LDL uptake comparable to primary endothelial cells (EC). RNA sequencing (RNAseq) revealed a robust correlation coefficient between iECs and EC (R = 0.76), whereas gene responses to smoke were qualitatively nearly identical between iECs and primary ECs (R=0.86). Further analysis of transcriptional responses implicated eighteen transcription factors in regulating responses to smoke treatment, and identified gene sets regulated by each transcription factor, including oxidative stress, DNA damage/repair, ER stress, apoptosis, and cell cycle arrest. Assays for 42 cytokines in HUVEC cells and iECs identified 23 cytokines that responded dynamically to cigarette smoke. These cytokines and cellular stress response pathways describe endothelial responses for lymphocyte attachment, activation of coagulation and complement, lymphocyte growth factors, and inflammation and fibrosis; EC-initiated events that collectively lead to atherosclerosis. Thus, these studies validate the iEC model and identify transcriptional response networks by which ECs respond to tobacco smoke. Our results systematically trace how ECs use these response networks to regulate genes and pathways, and finally cytokine signals to other cells, to initiate the diverse processes that lead to atherosclerosis and cardiovascular disease.
2020-04-20 | GSE141136 | GEO
Project description:Exposure to secondhand tobacco smoke during early childhood has been linked with an increased risk for behavioral disorders, yet little is known regarding how brain development is impacted. Using an environmental tobacco smoke (ETS) passive inhalation model, this study assesses the neurodevelopmental impact of juvenile exposure during a critical period of frontal cortex development, specifically that of the rat orbital neocortex between postnatal days 8 and 22. Agnostic shotgun proteomics was employed to discern the biomolecular shift within this rapidly developing brain region that is responsible for higher-order behavioral control. The orbital cortex neuroproteome was assessed between ETS-exposed and room-air control animals employing a label-free shotgun approach with data-independent acquisition. Following protein roll-up, a total of X protein were found statistically altered in quantity out of Y total proteins identified. These results implicate a prominent shift within metabolic processes and synaptic organization related to excitatory and inhibitory neurotransmission. Findings derived from this dataset may further our understanding of how secondhand smoke exposure can perturb the orbital frontal cortex and result in developmental behavioral disorders.
2018-12-17 | PXD011744 | Pride
Project description:Exposure to secondhand tobacco smoke during early childhood has been linked with an increased risk for behavioral disorders, yet little is known regarding how brain development is impacted. Using an environmental tobacco smoke (ETS) passive inhalation model, this study assesses the neurodevelopmental impact of juvenile exposure during a critical period of frontal cortex development, specifically that of the rat orbital neocortex between postnatal days 8 and 22. Agnostic shotgun proteomics was employed to discern the biomolecular shift within this rapidly developing brain region that is responsible for higher-order behavioral control. The orbital cortex neuroproteome was assessed between ETS-exposed and room-air control animals employing a label-free shotgun approach with data-independent acquisition. Following protein roll-up, a total of X protein were found statistically altered in quantity out of Y total proteins identified. These results implicate a prominent shift within metabolic processes and synaptic organization related to excitatory and inhibitory neurotransmission. Findings derived from this dataset may further our understanding of how secondhand smoke exposure can perturb the orbital frontal cortex and result in developmental behavioral disorders.
2020-05-26 | PXD007690 | Pride
Project description:Background: Healthy individuals exposed to low levels of cigarette smoke have a decrement in lung function and higher risk for lung disease compared to unexposed individuals. We hypothesized that healthy individuals exposed to low levels of tobacco smoke must have biologic changes in the small airway epithelium compared to healthy unexposed individuals. Methods: Small airway epithelium was obtained by bronchoscopy from 121 individuals; microarrays assessed genome wide gene expression, and urine nicotine and cotinine were used to categorized subjects as “nonsmokers,” “active smokers,” and “low exposure.” The gene expression data was used to determine the threshold and ID50 of urine nicotine and cotinine at which the small airway epithelium showed abnormal responses. Results: There was no threshold of urine nicotine without an abnormal small airway epithelial response, and only a slightly above detectable threshold abnormal response for cotinine. The nicotine ID50 for nicotine was 25 ng/ml and cotinine 104 ng/ml. Conclusions: The small airway epithelium detects and responds to low levels of tobacco smoke with transcriptome modifications. This provides biologic correlates of epidemiologic studies linking low level tobacco smoke exposure to lung health risk, health, identifies genes in the lung cells most sensitive to tobacco smoke and defines thresholds at the lung epithelium responds to inhaled tobacco smoke.
2011-02-02 | GSE19667 | GEO
Project description:We have examined the impact of subchronic levels of tobacoo smoke on murine lungs. We have used high density DNA microarray and analysed lung tissues from mice exposed to mainstream tobacco smoke (MTS). Our results reveal induction of inflammatory cytokine interleukin-6 (IL-6) and its antagonist suppressor of cytokine signalling (SOCS3) mRNA in smoking group. We also show that these changes are transient and are reversed completely after a period of cessation of smoking. Experiment Overall Design: Male C57B1/CBA mice were exposed to MTS from two cigarettes daily, 5 days/week for 6 or 12 weeks. Mice were sacrificed immediately, or six weeks following the last cigarette. Left lung lobes were removed and flash frozen. Total RNA was isolated from a small part of the frozen lung and was hybridized against universal mouse reference RNA to Agilent Oligo DNA microarrays (Agilent Technologies) containing 22,000 transcripts. Microarrays were normalized using a global LOWESS approach and analyzed by MAANOVA 2.0 and SAM. Microarray results were validated by real time RT-PCR. Impact of alteration in expression of select genes was further validated by analysing their total protein levels in lung tissue homogenates.
2009-09-18 | E-GEOD-12930 | biostudies-arrayexpress
Project description:In addition to being causally linked to the formation of multiple tumor types, tobacco use has been associated with decreased anticancer treatment efficacy and reduced survival time. A detailed understanding of the cellular mechanisms that are affected by tobacco smoke should facilitate the development of improved preventive and therapeutic strategies. We have investigated the effects of a tobacco smoke (TS) extract on the transcriptome of MSK-Leuk1 cells, a cellular model of oral leukoplakia. Using Affymetrix HGU133 Plus 2 arrays, 411 differentially expressed probesets were identified. The observed transcriptome changes were grouped according to functional information, and translated into molecular interaction network maps and signaling pathways. Pathways related to cellular proliferation, inflammation, apoptosis and tissue injury appeared to be perturbed. Analysis of networks connecting the affected genes identified specific molecular interactions, hubs and key transcription regulators affected by TS. Thus TS was found to induce several EGFR ligands forming an EGFR-centered molecular interaction network, as well as several AhR-dependent genes, including the xenobiotic metabolizing enzymes CYP1A1 and CYP1B1. Notably, the latter findings in vitro are consistent with our parallel finding that levels of CYP1A1 and CYP1B1 were increased in oral mucosa of smokers. Collectively, these results offer insights into the mechanisms underlying the procarcinogenic effects of TS and raise the possibility that inhibitors of EGFR or AhR signaling will prevent or delay the development of tobacco smoke-related tumors. Moreover, the inductive effects of TS on xenobiotic metabolizing enzymes may help explain reduced efficacy of chemotherapy, and suggest targets for chemopreventive agents in smokers. Experiment Overall Design: In this study MSK-Leuk1 cells established from a dysplastic leukoplakia lesion adjacent to a squamous cell carcinoma of the tongue were exposed to tobacco condensate for 0.5 hr, 3 hr, 6 hr, 12 hr and 24 hr, respectively and compared to untreated controls. Six biological replicates were used at each timepoint for each condition (Control or Tobacco Smoke treated).
2008-10-21 | E-GEOD-10063 | biostudies-arrayexpress