Article: Cigarette smoke activates the parthanatos pathway of cell death in human bronchial epithelial cells.
Cell death discovery
2019 Volume 5, Page(s) 127
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 ...
| 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. |
|---|---|
| Language | English |
| Publishing date | 2019-08-05 |
| Publishing country | United States |
| Document type | Journal Article |
| ISSN | 2058-7716 |
| ISSN | 2058-7716 |
| DOI | 10.1038/s41420-019-0205-3 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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