Protective Action of 3,5-Diiodo-L-Thyronine on Cigarette Smoke-Induced Mitochondrial Dysfunction in Human Alveolar Epithelial Cells
<b>Background</b>: Cigarette smoke (CS) is a major risk factor for chronic lung conditions. Oxidative stress and mitochondrial dysfunction play a crucial role in CS-induced pulmonary injury. 3,5-Diiodothyronine (T2) affects energy metabolism, having mitochondria as a major target. Howeve...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-04-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/5/1014 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850127260520022016 |
|---|---|
| author | Francesca Panico Davida Mirra Giuseppe Petito Giuseppe Spaziano Vitale Del Vecchio Renata Esposito Rosalba Senese Vincenzo Desiderio Antonia Lanni Bruno D’Agostino |
| author_facet | Francesca Panico Davida Mirra Giuseppe Petito Giuseppe Spaziano Vitale Del Vecchio Renata Esposito Rosalba Senese Vincenzo Desiderio Antonia Lanni Bruno D’Agostino |
| author_sort | Francesca Panico |
| collection | DOAJ |
| description | <b>Background</b>: Cigarette smoke (CS) is a major risk factor for chronic lung conditions. Oxidative stress and mitochondrial dysfunction play a crucial role in CS-induced pulmonary injury. 3,5-Diiodothyronine (T2) affects energy metabolism, having mitochondria as a major target. However, the underlying mechanisms of T2 related to lung diseases are poorly understood. <b>Aims</b>: To investigate the protective action of T2 on CS-induced mitochondrial dysfunction in an in vitro model of human epithelial alveolar cells. <b>Methods</b>: ATP synthesis and cytochrome c oxidase (COX) activity, as a marker of mitochondrial function, was assessed in A549 cells pretreated with T2 and exposed to CS using a bioluminescence assay and an Oroboros 2k-Oxygraph system, respectively. An evaluation of the oxidative status was conducted by assessing superoxide radical production, superoxide dismutase (SOD) activity, and H<sub>2</sub>O<sub>2</sub> levels. Moreover, we investigated the mitochondrial mass via Mito-Tracker Green (MTG) staining and flow cytometry analysis. <b>Results</b>: CS significantly reduced ATP production. T2 pretreatment was found to prevent CS-induced impairments in ATP synthesis, enhancing COX activity. Additionally, the 2 h T2 pretreatment of CS-exposed cells mitigated CS-induced oxidative stress, thereby enhancing SOD activity and reducing the superoxide anion and H<sub>2</sub>O<sub>2</sub> levels. Finally, MTG labeling was correlated with CS-induced mitochondrial mass gain, which is associated with cell senescence. Unexpectedly, T2 was not able to significantly prevent this mass increment, probably due to its rapid mode of action. <b>Conclusions</b>: Our results provide new insights into the protective effects of T2 against CS-induced mitochondrial damage. |
| format | Article |
| id | doaj-art-ffad939db4de4838bc25a7b99c6ae584 |
| institution | OA Journals |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-ffad939db4de4838bc25a7b99c6ae5842025-08-20T02:33:43ZengMDPI AGBiomedicines2227-90592025-04-01135101410.3390/biomedicines13051014Protective Action of 3,5-Diiodo-L-Thyronine on Cigarette Smoke-Induced Mitochondrial Dysfunction in Human Alveolar Epithelial CellsFrancesca Panico0Davida Mirra1Giuseppe Petito2Giuseppe Spaziano3Vitale Del Vecchio4Renata Esposito5Rosalba Senese6Vincenzo Desiderio7Antonia Lanni8Bruno D’Agostino9Department of Health Sciences, Magna Græcia University, 88100 Catanzaro, ItalyDepartment of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, 81100 Caserta, ItalyDepartment of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, 81100 Caserta, ItalyDepartment of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, 81100 Caserta, ItalyDepartment of Experimental Medicine, Histology and Embryology Section, University of Campania “L. Vanvitelli”, 80138 Naples, ItalyDepartment of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, 81100 Caserta, ItalyDepartment of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, 81100 Caserta, ItalyDepartment of Experimental Medicine, Histology and Embryology Section, University of Campania “L. Vanvitelli”, 80138 Naples, ItalyDepartment of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, 81100 Caserta, ItalyDepartment of Environmental Biological and Pharmaceutical Sciences and Technologies, University of Campania Luigi Vanvitelli, 81100 Caserta, Italy<b>Background</b>: Cigarette smoke (CS) is a major risk factor for chronic lung conditions. Oxidative stress and mitochondrial dysfunction play a crucial role in CS-induced pulmonary injury. 3,5-Diiodothyronine (T2) affects energy metabolism, having mitochondria as a major target. However, the underlying mechanisms of T2 related to lung diseases are poorly understood. <b>Aims</b>: To investigate the protective action of T2 on CS-induced mitochondrial dysfunction in an in vitro model of human epithelial alveolar cells. <b>Methods</b>: ATP synthesis and cytochrome c oxidase (COX) activity, as a marker of mitochondrial function, was assessed in A549 cells pretreated with T2 and exposed to CS using a bioluminescence assay and an Oroboros 2k-Oxygraph system, respectively. An evaluation of the oxidative status was conducted by assessing superoxide radical production, superoxide dismutase (SOD) activity, and H<sub>2</sub>O<sub>2</sub> levels. Moreover, we investigated the mitochondrial mass via Mito-Tracker Green (MTG) staining and flow cytometry analysis. <b>Results</b>: CS significantly reduced ATP production. T2 pretreatment was found to prevent CS-induced impairments in ATP synthesis, enhancing COX activity. Additionally, the 2 h T2 pretreatment of CS-exposed cells mitigated CS-induced oxidative stress, thereby enhancing SOD activity and reducing the superoxide anion and H<sub>2</sub>O<sub>2</sub> levels. Finally, MTG labeling was correlated with CS-induced mitochondrial mass gain, which is associated with cell senescence. Unexpectedly, T2 was not able to significantly prevent this mass increment, probably due to its rapid mode of action. <b>Conclusions</b>: Our results provide new insights into the protective effects of T2 against CS-induced mitochondrial damage.https://www.mdpi.com/2227-9059/13/5/1014cigarette smokemitochondrial dysfunction3,5-diiodo-L-thyroninealveolar epithelial cellsoxidative stress |
| spellingShingle | Francesca Panico Davida Mirra Giuseppe Petito Giuseppe Spaziano Vitale Del Vecchio Renata Esposito Rosalba Senese Vincenzo Desiderio Antonia Lanni Bruno D’Agostino Protective Action of 3,5-Diiodo-L-Thyronine on Cigarette Smoke-Induced Mitochondrial Dysfunction in Human Alveolar Epithelial Cells Biomedicines cigarette smoke mitochondrial dysfunction 3,5-diiodo-L-thyronine alveolar epithelial cells oxidative stress |
| title | Protective Action of 3,5-Diiodo-L-Thyronine on Cigarette Smoke-Induced Mitochondrial Dysfunction in Human Alveolar Epithelial Cells |
| title_full | Protective Action of 3,5-Diiodo-L-Thyronine on Cigarette Smoke-Induced Mitochondrial Dysfunction in Human Alveolar Epithelial Cells |
| title_fullStr | Protective Action of 3,5-Diiodo-L-Thyronine on Cigarette Smoke-Induced Mitochondrial Dysfunction in Human Alveolar Epithelial Cells |
| title_full_unstemmed | Protective Action of 3,5-Diiodo-L-Thyronine on Cigarette Smoke-Induced Mitochondrial Dysfunction in Human Alveolar Epithelial Cells |
| title_short | Protective Action of 3,5-Diiodo-L-Thyronine on Cigarette Smoke-Induced Mitochondrial Dysfunction in Human Alveolar Epithelial Cells |
| title_sort | protective action of 3 5 diiodo l thyronine on cigarette smoke induced mitochondrial dysfunction in human alveolar epithelial cells |
| topic | cigarette smoke mitochondrial dysfunction 3,5-diiodo-L-thyronine alveolar epithelial cells oxidative stress |
| url | https://www.mdpi.com/2227-9059/13/5/1014 |
| work_keys_str_mv | AT francescapanico protectiveactionof35diiodolthyronineoncigarettesmokeinducedmitochondrialdysfunctioninhumanalveolarepithelialcells AT davidamirra protectiveactionof35diiodolthyronineoncigarettesmokeinducedmitochondrialdysfunctioninhumanalveolarepithelialcells AT giuseppepetito protectiveactionof35diiodolthyronineoncigarettesmokeinducedmitochondrialdysfunctioninhumanalveolarepithelialcells AT giuseppespaziano protectiveactionof35diiodolthyronineoncigarettesmokeinducedmitochondrialdysfunctioninhumanalveolarepithelialcells AT vitaledelvecchio protectiveactionof35diiodolthyronineoncigarettesmokeinducedmitochondrialdysfunctioninhumanalveolarepithelialcells AT renataesposito protectiveactionof35diiodolthyronineoncigarettesmokeinducedmitochondrialdysfunctioninhumanalveolarepithelialcells AT rosalbasenese protectiveactionof35diiodolthyronineoncigarettesmokeinducedmitochondrialdysfunctioninhumanalveolarepithelialcells AT vincenzodesiderio protectiveactionof35diiodolthyronineoncigarettesmokeinducedmitochondrialdysfunctioninhumanalveolarepithelialcells AT antonialanni protectiveactionof35diiodolthyronineoncigarettesmokeinducedmitochondrialdysfunctioninhumanalveolarepithelialcells AT brunodagostino protectiveactionof35diiodolthyronineoncigarettesmokeinducedmitochondrialdysfunctioninhumanalveolarepithelialcells |