CSE-Induced ER-Mitochondria Crosstalk Promotes Oxidative Stress and Impairs Bronchial Contractile Response
Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking, is among the most prevalent diseases worldwide. Previous studies have shown that cigarette smoke extract (CSE) can directly affect pulmonary artery function independently of hypoxia resulting from the airway o...
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MDPI AG
2025-06-01
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| Series: | Antioxidants |
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| author | Jorge Rodríguez-Pérez Rosa Andreu-Martínez Leila Pérez-Sánchez Ana Hernández-García Cecilia Muñoz-Calleja Ángel Cogolludo María J. Calzada |
| author_facet | Jorge Rodríguez-Pérez Rosa Andreu-Martínez Leila Pérez-Sánchez Ana Hernández-García Cecilia Muñoz-Calleja Ángel Cogolludo María J. Calzada |
| author_sort | Jorge Rodríguez-Pérez |
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| description | Chronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking, is among the most prevalent diseases worldwide. Previous studies have shown that cigarette smoke extract (CSE) can directly affect pulmonary artery function independently of hypoxia resulting from the airway obstruction. In addition, CSE also affects bronchial smooth muscle, leading to airway hyper-responsiveness. However, its specific impact on the contractile machinery of this compartment remains unclear. In this study, using in vitro experiments with human bronchial smooth muscle cells (hBSMCs), we found that CSE exposure disrupted calcium homeostasis, increased ROS and lipid peroxidation, and reduced cell antioxidant defenses. Furthermore, CSE exposure altered the cell contractile apparatus by decreasing key cytoskeletal proteins and impairing actin dynamics, potentially contributing to the dysregulated contractile response of cells. Notably, these effects were significantly attenuated by antioxidant drugs such as mitoTEMPO and N-acetylcysteine, as well as by the inhibition of the endoplasmic reticulum (ER) calcium channels with 2-aminoethoxydiphenyl borate (2-APB). More importantly, mitoTEMPO partially restored the contractile response of bronchus upon CSE challenge. Collectively, our findings give evidence that CSE-mediated increase in ROS and intracellular calcium contribute to cytoskeletal disruption and functional impairment in airway smooth muscle. Moreover, these results also point to potential therapeutical approaches for mitigating the harmful effects of cigarette smoke in the lung. |
| format | Article |
| id | doaj-art-e252d09fc3644f0a8dcceb989637adce |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-e252d09fc3644f0a8dcceb989637adce2025-08-20T02:24:17ZengMDPI AGAntioxidants2076-39212025-06-0114670310.3390/antiox14060703CSE-Induced ER-Mitochondria Crosstalk Promotes Oxidative Stress and Impairs Bronchial Contractile ResponseJorge Rodríguez-Pérez0Rosa Andreu-Martínez1Leila Pérez-Sánchez2Ana Hernández-García3Cecilia Muñoz-Calleja4Ángel Cogolludo5María J. Calzada6Departamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, SpainDepartamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, SpainDepartamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, SpainDepartamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, SpainDepartamento de Farmacología y Toxicología, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, SpainDepartamento de Medicina, Facultad de Medicina, Universidad Autónoma de Madrid, 28049 Madrid, SpainChronic obstructive pulmonary disease (COPD), whose main risk factor is cigarette smoking, is among the most prevalent diseases worldwide. Previous studies have shown that cigarette smoke extract (CSE) can directly affect pulmonary artery function independently of hypoxia resulting from the airway obstruction. In addition, CSE also affects bronchial smooth muscle, leading to airway hyper-responsiveness. However, its specific impact on the contractile machinery of this compartment remains unclear. In this study, using in vitro experiments with human bronchial smooth muscle cells (hBSMCs), we found that CSE exposure disrupted calcium homeostasis, increased ROS and lipid peroxidation, and reduced cell antioxidant defenses. Furthermore, CSE exposure altered the cell contractile apparatus by decreasing key cytoskeletal proteins and impairing actin dynamics, potentially contributing to the dysregulated contractile response of cells. Notably, these effects were significantly attenuated by antioxidant drugs such as mitoTEMPO and N-acetylcysteine, as well as by the inhibition of the endoplasmic reticulum (ER) calcium channels with 2-aminoethoxydiphenyl borate (2-APB). More importantly, mitoTEMPO partially restored the contractile response of bronchus upon CSE challenge. Collectively, our findings give evidence that CSE-mediated increase in ROS and intracellular calcium contribute to cytoskeletal disruption and functional impairment in airway smooth muscle. Moreover, these results also point to potential therapeutical approaches for mitigating the harmful effects of cigarette smoke in the lung.https://www.mdpi.com/2076-3921/14/6/703COPDcigarette smokecontractilitymitochondriacalciumROS |
| spellingShingle | Jorge Rodríguez-Pérez Rosa Andreu-Martínez Leila Pérez-Sánchez Ana Hernández-García Cecilia Muñoz-Calleja Ángel Cogolludo María J. Calzada CSE-Induced ER-Mitochondria Crosstalk Promotes Oxidative Stress and Impairs Bronchial Contractile Response Antioxidants COPD cigarette smoke contractility mitochondria calcium ROS |
| title | CSE-Induced ER-Mitochondria Crosstalk Promotes Oxidative Stress and Impairs Bronchial Contractile Response |
| title_full | CSE-Induced ER-Mitochondria Crosstalk Promotes Oxidative Stress and Impairs Bronchial Contractile Response |
| title_fullStr | CSE-Induced ER-Mitochondria Crosstalk Promotes Oxidative Stress and Impairs Bronchial Contractile Response |
| title_full_unstemmed | CSE-Induced ER-Mitochondria Crosstalk Promotes Oxidative Stress and Impairs Bronchial Contractile Response |
| title_short | CSE-Induced ER-Mitochondria Crosstalk Promotes Oxidative Stress and Impairs Bronchial Contractile Response |
| title_sort | cse induced er mitochondria crosstalk promotes oxidative stress and impairs bronchial contractile response |
| topic | COPD cigarette smoke contractility mitochondria calcium ROS |
| url | https://www.mdpi.com/2076-3921/14/6/703 |
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