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Cigarette smoke activates the parthanatos pathway of cell death in human bronchial epithelial cells.

ABSTRACT: Tobacco smoke negatively affects human bronchial epithelial (HBE) cells and is directly implicated in the etiology of smoking related respiratory diseases. Smoke exposure causes double-stranded DNA breaks and DNA damage activates PARP-1, the key mediator of the parthanatos pathway of cell death. We hypothesize that smoke exposure activates the parthanatos pathway in HBE cells and represents a cell death mechanism that contributes to smoking related lung diseases. We exposed fully differentiated, primary HBE cells grown at the air liquid interface to cigarette smoke and evaluated them for parthanatos pathway activation. Smoke exposure induced mitochondrial to nuclear translocation of Apoptosis-Inducing Factor (AIF) and Endonuclease G (EndoG) within the first three hours characteristic of the parthanatos pathway. Exposing cells to an increasing number of cigarettes revealed that significant activation of the parthanatos pathway occurs after exposure to higher levels of smoke. Use of the specific PARP-1 inhibitor, BMN673, abrogated the effect of smoke induced activation of the parthanatos pathway. Smoke-mediated activation of the parthanatos pathway is increased in HBE cells originating from habitual smokers compared to non-smokers. This suggests that chronic smoke exposure leads to an increase in smoke-mediated activation of the parthanatos pathway and implicates its contribution in the pathogenesis of smoke-related lung diseases.

SUBMITTER: Kunzi L

PROVIDER: S-EPMC6683143 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Cigarette smoke activates the parthanatos pathway of cell death in human bronchial epithelial cells.

Künzi Lisa L Holt Gregory E GE

Cell death discovery 20190805

Tobacco smoke negatively affects human bronchial epithelial (HBE) cells and is directly implicated in the etiology of smoking related respiratory diseases. Smoke exposure causes double-stranded DNA breaks and DNA damage activates PARP-1, the key mediator of the parthanatos pathway of cell death. We hypothesize that smoke exposure activates the parthanatos pathway in HBE cells and represents a cell death mechanism that contributes to smoking related lung diseases. We exposed fully differentiated, ...[more]

PMID: 31396404

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Project description:Chronic obstructive pulmonary disease (COPD) is a prevalent and long-term airway disease. It has been reported that fucoxanthin (FX) exhibits anti-inflammatory and antioxidant effects. However, the underlying mechanism of FX in COPD remains unknown. Therefore, to investigate the effect of FX on COPD, BEAS-2B cells were treated with cigarette smoke extract (CSE). The viability of BEAS-2B cells treated with increasing doses of FX was assessed by Cell Counting Kit-8. Lactate dehydrogenase (LDH) levels were measured using a corresponding kit. In addition, ELISA was carried out to detect the content of TNF-α, IL-1β and IL-6. Additionally, a TUNEL assay and western blot analysis were performed to assess the cell apoptosis rate. Furthermore, 2',7'-dichlorodihydrofluorescein diacetate was used to measure reactive oxygen species levels, while the contents of oxidative stress-associated indexes were determined using the corresponding kits. Bioinformatics analysis using the search tool for interactions of chemicals database predicted that peroxisome proliferator-activated receptor γ (PPARγ) may be a target of FX. The binding capacity of FTX with PPARγ was confirmed by molecular docking. The protein expression levels of the PPARγ/NF-κB signaling-associated factors were detected by western blot analysis. Finally, the regulatory mechanism of FX in COPD was revealed following cell treatment with the PPARγ inhibitor, T0070907. The results demonstrated that FX enhanced CSE-induced BEAS-2B cell viability and attenuated CSE-induced BEAS-2B cell inflammation and oxidative damage, possibly via triggering PPARγ/NF-κB signaling. Pre-treatment of BEAS-2B cells with the PPARγ inhibitor, T0070907, could reverse the protective effects of FX on CSE-induced BEAS-2B cells. Overall, the present study suggested that FX could ameliorate oxidative damage as well as inflammation in CSE-treated human bronchial epithelial in patients with COPD via modulating the PPARγ/NF-κB signaling pathway.

Dataset Information

Cigarette smoke activates the parthanatos pathway of cell death in human bronchial epithelial cells.

Publications

Cigarette smoke activates the parthanatos pathway of cell death in human bronchial epithelial cells.

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