Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA113355 | ENA |
REPOSITORIES: ENA
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Project description:Proteasome dysfunction is emerging as a novel pathomechanism for the development of chronic obstructive pulmonary disease (COPD), a major leading cause of death in the world. Cigarette smoke is one of the main risk factors for COPD and has been shown to impair proteasome function in vitro and in vivo. Importantly, proteasome activity is inhibited in COPD lungs while expression levels of proteasome subunits are not altered. In the present study, we dissected the molecular changes induced by cigarette smoke on proteasome function in lung epithelial cells and mouse lungs. We analyzed the integrity, composition, and the interactome of isolated 26S proteasome complexes from smoke-exposed cells and mouse lungs. Moreover, we applied native MS analysis to investigate whether reactive compounds of cigarette smoke directly modify and inhibit the 20S proteasome complex. Our data reveal that the 20S proteasome is slightly destabilized in the absence of any dominant modification of proteasomal proteins. 26S pulldown and stoichiometry analysis indicated that 26S proteasome complexes become instable in response to cigarette smoke exposure. Of note, the interactome of the 26S was clearly altered in smoke-exposed mouse lungs possibly reflecting an altered cellular composition in the lungs of the smoke-exposed mice. Taken together, our results suggest that cigarette smoke induces minor but detectable changes in the stability and interactome of 20S and 26S proteasome complexes which might contribute in a chronic setting to imbalanced proteostasis as observed in chronic lung diseases associated with cigarette smoking.
2019-01-08 | PXD007148 | Pride
Project description:Cigarette smoke is the most relevant risk factor for the development of lung cancer and chronic obstructive pulmonary disease. Many of its more than 4500 chemicals are highly reactive, thereby altering protein structure and function. Here, we used subcellular fractionation coupled to label-free quantitative MS to globally assess alterations in the proteome of different compartments of lung epithelial cells upon exposure to cigarette smoke extract. Proteomic profiling of the human alveolar derived cell line A549 revealed the most pronounced changes within the cellular secretome with preferential downregulation of proteins involved in wound healing and extracellular matrix organization. In particular, secretion of secreted protein acidic and rich in cysteine, a matricellular protein that functions in tissue response to injury, was consistently diminished by cigarette smoke extract in various pulmonary epithelial cell lines and primary cells of human and mouse origin as well as in mouse ex vivo lung tissue cultures. Our study reveals a previously unrecognized acute response of lung epithelial cells to cigarette smoke that includes altered secretion of proteins involved in extracellular matrix organization and wound healing. This may contribute to sustained alterations in tissue remodeling as observed in lung cancer and chronic obstructive pulmonary disease.
2019-01-08 | PXD007180 | Pride
Project description:To profile lung miRNA expression in our mouse model of cigarette smoke-induced chronic obstructive pulmonary disease, we employed the Agilent unrestricted Mouse miRNA (8 x 15k arrays per slide, AMADID Number: 021828, Sanger Version 12) platform as a discovery tool to identify miRNAs of interest in the development of experimental chronic obstructive pulmonary disease. Mice were exposed to cigarette smoke (or room air) for 4, 6, 8, 12 weeks, lungs were excised, and total RNA isolated.
2021-11-05 | GSE186955 | GEO
Project description:Cigarette smoking remains the leading cause of non-small cell lung carcinoma. Studies involving acute exposure of smoke on lung cells revealed induction of pre- cancerous state in lung cells. Recently few studies have reported the chronic effect of cigarette smoke in inducing cellular transformation. Yet no systemic study has been performed to understand the molecular alterations in lung cells due to cigarette smoke. Hence it is both important and necessary to study the chronic effect of cigarette smoke in a temporal setting to understand the molecular alterations. In this study, we carried out TMT based proteomic profiling of lung cells which were exposed to cigarette smoke condensate (CSC) for upto 12 months. We identified 2621 proteins in total, of which 145, 114, 87, 169 and 671 proteins were differentially expressed (p<0.05, 1.5 fold) in 2nd, 4th, 6th, 8th and 12th month respectively. Pathway analysis revealed enrichment of xenobiotic metabolism signaling for the first 8 months of smoke treatment, where as continued exposure of smoke for 12 months revealed mitochondrial reprogramming in cells which includes dysregulation of oxidative phosphorylation machinery leading to enhanced reactive oxygen species and higher expression of enzymes involved in tricarboxylic acid cycle (TCA). In addition, chronic exposure of smoke led to overexpression of enzymes involved in glutamine metabolism, fatty acid degradation and lactate synthesis. This could possibly explain the availability of alternative source of carbon in TCA cycle apart from glycolytic pyruvate. Our data indicates that chronic exposure to cigarette smoke induces mitochondrial metabolic transformation in cells to support growth and survival.
2022-03-02 | PXD007108 | Pride
Project description:Cigarette smoke has been associated with the development of various lung diseases including cancer. Dysregulation of miRNAs is known to affect protein expression which leads to diverse functional consequences. Investigating miRNA and protein expression in response to cigarette smoke exposure can lead to the identification of potential therapeutic and chemopreventive targets. We employed a SILAC-based quantitative proteomic analysis to identify proteins differentially expressed in response to cigarette smoke in H292 lung cancer cells. LC-MS/MS analysis led to the identification of 3,959 proteins, of which, 303 proteins were overexpressed and 112 proteins were found to be downregulated in cigarette smoke-treated H292 cells.
2018-10-25 | PXD003086 | Pride
Project description:<p>Background: Chronic obstructive pulmonary disease (COPD) is a progressive inflammatory disorder with rising global morbidity and mortality. Emerging evidence suggests that systemic metabolic alterations, particularly dyslipidemia, contribute to COPD pathogenesis. However, the mechanisms linking lipid dysregulation to pulmonary inflammation and tissue injury remain poorly defined.</p><p>Methods: Untargeted metabolomic profiling was performed on plasma samples from healthy individuals and patients with COPD to identify disease associated metabolic alterations. A high-cholesterol diet (HCD) mouse model, with or without chronic cigarette smoke exposure, was used to examine the impact of systemic cholesterol elevation on lung structure and inflammation. Complementary in vitro studies using THP-1 derived and bone marrow derived macrophages were conducted to investigate mitochondrial function, ROS generation, and downstream signaling pathways. Transcriptomic analyses were employed to identify key molecular mediators.</p><p>Results: Plasma metabolomics revealed significant dysregulation of lipid metabolism in COPD, with elevated cholesterol levels correlating inversely with lung function. In vivo, HCD feeding induced pulmonary inflammation and further exacerbated cigarette smoke induced lung tissue destruction. In macrophages, combined cholesterol loading and cigarette smoke extraction treatment disrupted mitochondrial integrity, reduced respiratory capacity, and increase ROS generation. Elevated ROS levels upregulated PPIA, which in turn activated NF-κB signaling and promoted IL-1β secretion. Silencing PPIA or inhibiting ROS significantly attenuated NF-κB activation and cytokine release. Consistent with these findings, increased PPIA expression and NF-κB phosphorylation were observed in lungs of HCD-fed, cigarette smoke exposed mice, and PPIA levels were elevated in bronchoalveolar lavage fluid from COPD patients.</p>
2025-11-26 | MTBLS13388 | MetaboLights
Project description:Lung cancer remains a major contributor to cancer fatalities, with cigarette smoking known to be responsible for up to 80% of cases. Based on the ability of cigarette smoke to induce inflammation in the lungs and increased lung cancer incidence in smokers with inflammatory conditions such as COPD, we hypothesized that inflammation plays an important role in carcinogenicity of cigarette smoke. In order to test this hypothesis, we performed multi-omic analyses of Type II pneumocytes of A/J mice exposed to cigarette smoke for various time periods. We found that cigarette smoke exposure resulted in significant changes in DNA methylation and hydroxymethylation, gene expression patterns, and protein abundance that were partially reversible and contributed to an inflammatory and potentially oncogenic phenotype.
2024-09-18 | GSE275545 | GEO
Project description:Expression data from adult mouse testis exposed to cigarette smoke in utero
| PRJNA223381 | ENA
Project description:Expression data from adult mouse ovaries exposed to cigarette smoke in vivo
| PRJNA183706 | ENA
Project description:TGFβ inhibition attenuates chronic cigarette smoke induced lung injury and rescues lung architecture.
2011-12-30 | GSE33561 | GEO