Copper-Associated Oxidative Stress Contributes to Cellular Inflammatory Responses in Cystic Fibrosis
Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF Transmembrane Conductance Regulator (CFTR), an apical chloride channel. An early inflammation (EI) in the lung of CF patients occurring in the absence of any bacterial infection has been reported. This EI has been proposed to be...
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MDPI AG
2021-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/4/329 |
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| author | Amal Kouadri Johanna Cormenier Kevin Gemy Laurence Macari Peggy Charbonnier Pierre Richaud Isabelle Michaud-Soret Nadia Alfaidy Mohamed Benharouga |
| author_facet | Amal Kouadri Johanna Cormenier Kevin Gemy Laurence Macari Peggy Charbonnier Pierre Richaud Isabelle Michaud-Soret Nadia Alfaidy Mohamed Benharouga |
| author_sort | Amal Kouadri |
| collection | DOAJ |
| description | Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF Transmembrane Conductance Regulator (CFTR), an apical chloride channel. An early inflammation (EI) in the lung of CF patients occurring in the absence of any bacterial infection has been reported. This EI has been proposed to be associated with oxidative stress (OX-S), generated by deregulations of the oxidant/antioxidant status. Recently, we demonstrated that copper (Cu), an essential trace element, mediates OX-S in bronchial cells. However, the role of this element in the development of CF-EI, in association with OX-S, has never been investigated. Using healthy (16HBE14o-; HBE), CF (CFBE14o-; CFBE), and corrected-wild type CFTR CF (CFBE-wt) bronchial cells, we characterized the inflammation and OX-S profiles in relation to the copper status and CFTR expression and function. We demonstrated that CFBE cells exhibited a CFTR-independent intrinsic inflammation. These cells also exhibited an alteration in mitochondria, UPR (Unfolded Protein Response), catalase, Cu/Zn- and Mn-SOD activities, and an increase in the intracellular content of iron, zinc, and Cu. The increase in Cu concentration was associated with OX-S and inflammatory responses. These data identify cellular Cu as a key factor in the generation of CF-associated OX-S and opens new areas of investigation to better understand CF-associated EI. |
| first_indexed | 2024-03-10T12:56:55Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T12:56:55Z |
| publishDate | 2021-03-01 |
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| series | Biomedicines |
| spelling | doaj.art-40c21c30a05c4b91a3b2ffa7bfe5f3c02023-11-21T11:50:37ZengMDPI AGBiomedicines2227-90592021-03-019432910.3390/biomedicines9040329Copper-Associated Oxidative Stress Contributes to Cellular Inflammatory Responses in Cystic FibrosisAmal Kouadri0Johanna Cormenier1Kevin Gemy2Laurence Macari3Peggy Charbonnier4Pierre Richaud5Isabelle Michaud-Soret6Nadia Alfaidy7Mohamed Benharouga8Institut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie Pour la Santé, 38000 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie Pour la Santé, 38000 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie Pour la Santé, 38000 Grenoble, FranceCommissariat à l’Energie Atomique et Aux Energies Alternatives (CEA), 38000 Grenoble, FranceCommissariat à l’Energie Atomique et Aux Energies Alternatives (CEA), 38000 Grenoble, FranceCEA, CNRS, Institut de Biosciences et Biotechnologies d’Aix-Marseille (BIAM), Université Aix-Marseille, UMR 7265, CEA Cadarache, 13108 Saint-Paul-lez Durance, FranceCommissariat à l’Energie Atomique et Aux Energies Alternatives (CEA), 38000 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie Pour la Santé, 38000 Grenoble, FranceInstitut National de la Santé et de la Recherche Médicale U1292, Biologie et Biotechnologie Pour la Santé, 38000 Grenoble, FranceCystic fibrosis (CF) is caused by mutations in the gene encoding the CF Transmembrane Conductance Regulator (CFTR), an apical chloride channel. An early inflammation (EI) in the lung of CF patients occurring in the absence of any bacterial infection has been reported. This EI has been proposed to be associated with oxidative stress (OX-S), generated by deregulations of the oxidant/antioxidant status. Recently, we demonstrated that copper (Cu), an essential trace element, mediates OX-S in bronchial cells. However, the role of this element in the development of CF-EI, in association with OX-S, has never been investigated. Using healthy (16HBE14o-; HBE), CF (CFBE14o-; CFBE), and corrected-wild type CFTR CF (CFBE-wt) bronchial cells, we characterized the inflammation and OX-S profiles in relation to the copper status and CFTR expression and function. We demonstrated that CFBE cells exhibited a CFTR-independent intrinsic inflammation. These cells also exhibited an alteration in mitochondria, UPR (Unfolded Protein Response), catalase, Cu/Zn- and Mn-SOD activities, and an increase in the intracellular content of iron, zinc, and Cu. The increase in Cu concentration was associated with OX-S and inflammatory responses. These data identify cellular Cu as a key factor in the generation of CF-associated OX-S and opens new areas of investigation to better understand CF-associated EI.https://www.mdpi.com/2227-9059/9/4/329inflammationcystic fibrosisoxidative stressCFTRcopperlung |
| spellingShingle | Amal Kouadri Johanna Cormenier Kevin Gemy Laurence Macari Peggy Charbonnier Pierre Richaud Isabelle Michaud-Soret Nadia Alfaidy Mohamed Benharouga Copper-Associated Oxidative Stress Contributes to Cellular Inflammatory Responses in Cystic Fibrosis Biomedicines inflammation cystic fibrosis oxidative stress CFTR copper lung |
| title | Copper-Associated Oxidative Stress Contributes to Cellular Inflammatory Responses in Cystic Fibrosis |
| title_full | Copper-Associated Oxidative Stress Contributes to Cellular Inflammatory Responses in Cystic Fibrosis |
| title_fullStr | Copper-Associated Oxidative Stress Contributes to Cellular Inflammatory Responses in Cystic Fibrosis |
| title_full_unstemmed | Copper-Associated Oxidative Stress Contributes to Cellular Inflammatory Responses in Cystic Fibrosis |
| title_short | Copper-Associated Oxidative Stress Contributes to Cellular Inflammatory Responses in Cystic Fibrosis |
| title_sort | copper associated oxidative stress contributes to cellular inflammatory responses in cystic fibrosis |
| topic | inflammation cystic fibrosis oxidative stress CFTR copper lung |
| url | https://www.mdpi.com/2227-9059/9/4/329 |
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