ArticleTuberculosis and respiratory diseases2018
The Phosphodiesterase 4 Inhibitor Roflumilast Protects against Cigarette Smoke Extract-Induced Mitophagy-Dependent Cell Death in Epithelial Cells.
Article in Tuberculosis and respiratory diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 24 citations in OpenAlex.
- Steroids and flavonoids in TRQ ameliorates chronic obstructive pulmonary disease involving Pink1/Parkin-mediated mitophagy.Scientific reports · 2026Article
- SPG7-Mediated Regulation of mPTP and Mitochondrial Flickering in COPD: A Bioinformatics-Based Prediction of Mechanistic Framework.International journal of chronic obstructive pulmonary disease · 2026Article
- Mitophagy in idiopathic pulmonary fibrosis: from molecular mechanisms to therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- GNPAT/USP30 Stabilizes DRP1 Protein to Promote Mitochondrial Fission and Functional Damage in COPD Progression.The Kaohsiung journal of medical sciences · 2025Article
- Targeting selective autophagy and beyond: From underlying mechanisms to potential therapies.Journal of advanced research · 2024Review
- Autophagy/Mitophagy in Airway Diseases: Impact of Oxidative Stress on Epithelial Cells.Biomolecules · 2023Review
- Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway.Experimental and therapeutic medicine · 2023Article
- Investigation of apoptotic and autophagic effects of chronic roflumilast use on testicular tissue in rats by immunohistochemical and immunofluorescence methods.Iranian journal of basic medical sciences · 2023Article
- Review
- Cellular mitophagy: Mechanism, roles in diseases and small molecule pharmacological regulation.Theranostics · 2023Review
- Article
- The Multifaceted Roles of Autophagy in Infectious, Obstructive, and Malignant Airway Diseases.Biomedicines · 2022Review
- Acrolein inhalation acutely affects the regulation of mitochondrial metabolism in rat lung.Toxicology · 2022Article
- Dysregulated mitochondrial metabolism upon cigarette smoke exposure in various human bronchial epithelial cell models.Disease models & mechanisms · 2022Article
- DRP1-Mediated Mitochondrial Fission Regulates Lung Epithelial Response to Allergen.International journal of molecular sciences · 2021Article
- Chronic Obstructive Pulmonary Disease and Pulmonary Vascular Disease. A Comorbidity?Annals of the American Thoracic Society · 2018Review
- Phosphodiesterase-4 Inhibitors for the Treatment of Inflammatory Diseases.Frontiers in pharmacology · 2018Review
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5 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundRecent studies show that mitophagy, the autophagy-dependent turnover of mitochondria, mediates pulmonary epithelial cell death in response to cigarette smoke extract (CSE) exposure and contributes to the development of emphysema in vivo during chronic cigarette smoke (CS) exposure, although the underlying mechanisms remain unclear.
methodsIn this study, we investigated the role of mitophagy in the regulation of CSE-exposed lung bronchial epithelial cell (Beas-2B) death. We also investigated the role of a phosphodiesterase 4 inhibitor, roflumilast, in CSE-induced mitophagy-dependent cell death.
resultsOur results demonstrated that CSE induces mitophagy in Beas-2B cells through mitochondrial dysfunction and increased the expression levels of the mitophagy regulator protein, PTEN-induced putative kinase-1 (PINK1), and the mitochondrial fission protein, dynamin-1-like protein (DRP1). CSE-induced epithelial cell death was significantly increased in Beas-2B cells exposed to CSE but was decreased by small interfering RNA-dependent knockdown of DRP1. Treatment with roflumilast in Beas-2B cells inhibited CSE-induced mitochondrial dysfunction and mitophagy by inhibiting the expression of phospho-DRP1 and -PINK1. Roflumilast protected against cell death and increased cell viability, as determined by the lactate dehydrogenase release test and the MTT assay, respectively, in Beas-2B cells exposed to CSE.
conclusionThese findings suggest that roflumilast plays a protective role in CS-induced mitophagy-dependent cell death.
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