{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T13:50:57Z","timestamp":1790171457763,"version":"4.1.0"},"reference-count":32,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T00:00:00Z","timestamp":1749513600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministerio de Ciencia e Innovaci\u00f3n, Programa Retos en Investigaci\u00f3n","award":["139144OB-I00"],"award-info":[{"award-number":["139144OB-I00"]}]},{"name":"Spanish Ministerio de Ciencia e Innovaci\u00f3n, Programa Retos en Investigaci\u00f3n","award":["P2022\/BMD7224"],"award-info":[{"award-number":["P2022\/BMD7224"]}]},{"name":"Spanish Ministerio de Ciencia e Innovaci\u00f3n, Programa Retos en Investigaci\u00f3n","award":["convocatoria 2023"],"award-info":[{"award-number":["convocatoria 2023"]}]},{"name":"Redes en Biomedicina from Comunidad Autonoma of Madrid","award":["139144OB-I00"],"award-info":[{"award-number":["139144OB-I00"]}]},{"name":"Redes en Biomedicina from Comunidad Autonoma of Madrid","award":["P2022\/BMD7224"],"award-info":[{"award-number":["P2022\/BMD7224"]}]},{"name":"Redes en Biomedicina from Comunidad Autonoma of Madrid","award":["convocatoria 2023"],"award-info":[{"award-number":["convocatoria 2023"]}]},{"name":"Fundaci\u00f3n Eugenio Rodr\u00edguez Pascual","award":["139144OB-I00"],"award-info":[{"award-number":["139144OB-I00"]}]},{"name":"Fundaci\u00f3n Eugenio Rodr\u00edguez Pascual","award":["P2022\/BMD7224"],"award-info":[{"award-number":["P2022\/BMD7224"]}]},{"name":"Fundaci\u00f3n Eugenio Rodr\u00edguez Pascual","award":["convocatoria 2023"],"award-info":[{"award-number":["convocatoria 2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/antiox14060703","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T06:48:56Z","timestamp":1749538136000},"page":"703","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["CSE-Induced ER-Mitochondria Crosstalk Promotes Oxidative Stress and Impairs Bronchial Contractile Response"],"prefix":"10.3390","volume":"14","author":[{"given":"Jorge","family":"Rodr\u00edguez-P\u00e9rez","sequence":"first","affiliation":[{"name":"Departamento de Medicina, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Princesa (IIS-Princesa), 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Andreu-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Medicina, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Princesa (IIS-Princesa), 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leila","family":"P\u00e9rez-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Departamento de Medicina, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Princesa (IIS-Princesa), 28006 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2005-7077","authenticated-orcid":false,"given":"Ana","family":"Hern\u00e1ndez-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Mu\u00f1oz-Calleja","sequence":"additional","affiliation":[{"name":"Departamento de Medicina, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Princesa (IIS-Princesa), 28006 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1382-1698","authenticated-orcid":false,"given":"\u00c1ngel","family":"Cogolludo","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda y Toxicolog\u00eda, Facultad de Medicina, Universidad Complutense de Madrid, 28040 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda J.","family":"Calzada","sequence":"additional","affiliation":[{"name":"Departamento de Medicina, Facultad de Medicina, Universidad Aut\u00f3noma de Madrid, 28049 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria Princesa (IIS-Princesa), 28006 Madrid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, 28222 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"ITC17","DOI":"10.7326\/AITC202008040","article-title":"Chronic obstructive pulmonary disease","volume":"173","author":"Labaki","year":"2020","journal-title":"Ann. 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