Mdivi-1 alleviates nicotine-induced human periodontal ligament cells injury by inhibiting mitochondrial fission and dysfunction through the JNK/Drp1 pathway
Background: Nicotine, a major component of tobacco, is implicated in the pathogenesis of periodontitis. However, the exact mechanisms through which nicotine exerts its harmful effects remain incompletely understood. This study investigates the impact of nicotine-induced mitochondrial fission on huma...
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| Language: | English |
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Elsevier
2024-12-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324014143 |
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| author | Leihua Cui Meiqiao Chen Yihong Jin Huining Wang Yubo Hou |
| author_facet | Leihua Cui Meiqiao Chen Yihong Jin Huining Wang Yubo Hou |
| author_sort | Leihua Cui |
| collection | DOAJ |
| description | Background: Nicotine, a major component of tobacco, is implicated in the pathogenesis of periodontitis. However, the exact mechanisms through which nicotine exerts its harmful effects remain incompletely understood. This study investigates the impact of nicotine-induced mitochondrial fission on human periodontal ligament cells (hPDLCs). Methods: A range of assays, including MTT, immunofluorescence staining, flow cytometry, and western blotting, were utilized to evaluate hPDLC viability, apoptosis, mitochondrial fission, and function. Results: Nicotine decreases hPDLC viability in a dose-dependent manner, leading to apoptosis, an elevated BAX/BCL-2 ratio, and cellular injury. Furthermore, nicotine induces phosphorylation of Drp1 at Ser616, which facilitates mitochondrial fission, elevates mitochondrial ROS production, reduces mitochondrial membrane potential, and lowers ATP generation, resulting in mitochondrial dysfunction. Inhibition of Drp1 phosphorylation by Mdivi-1 significantly alleviates mitochondrial fission and dysfunction, reduces nicotine-induced apoptosis, and promotes osteogenic differentiation. Conclusion: Nicotine activates c-Jun N-terminal kinase (JNK), and the inhibition of JNK activity with SP600125 effectively prevents nicotine-induced mitochondrial fission, enhances cell viability, and inhibits Drp1 phosphorylation. |
| format | Article |
| id | doaj-art-da36ed8002a642e494615bfd8b56fd53 |
| institution | OA Journals |
| issn | 0147-6513 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-da36ed8002a642e494615bfd8b56fd532025-08-20T02:20:56ZengElsevierEcotoxicology and Environmental Safety0147-65132024-12-0128811733810.1016/j.ecoenv.2024.117338Mdivi-1 alleviates nicotine-induced human periodontal ligament cells injury by inhibiting mitochondrial fission and dysfunction through the JNK/Drp1 pathwayLeihua Cui0Meiqiao Chen1Yihong Jin2Huining Wang3Yubo Hou4Department of Oral Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Periodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Periodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, ChinaDepartment of Periodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Corresponding authors.Department of Periodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Corresponding authors.Background: Nicotine, a major component of tobacco, is implicated in the pathogenesis of periodontitis. However, the exact mechanisms through which nicotine exerts its harmful effects remain incompletely understood. This study investigates the impact of nicotine-induced mitochondrial fission on human periodontal ligament cells (hPDLCs). Methods: A range of assays, including MTT, immunofluorescence staining, flow cytometry, and western blotting, were utilized to evaluate hPDLC viability, apoptosis, mitochondrial fission, and function. Results: Nicotine decreases hPDLC viability in a dose-dependent manner, leading to apoptosis, an elevated BAX/BCL-2 ratio, and cellular injury. Furthermore, nicotine induces phosphorylation of Drp1 at Ser616, which facilitates mitochondrial fission, elevates mitochondrial ROS production, reduces mitochondrial membrane potential, and lowers ATP generation, resulting in mitochondrial dysfunction. Inhibition of Drp1 phosphorylation by Mdivi-1 significantly alleviates mitochondrial fission and dysfunction, reduces nicotine-induced apoptosis, and promotes osteogenic differentiation. Conclusion: Nicotine activates c-Jun N-terminal kinase (JNK), and the inhibition of JNK activity with SP600125 effectively prevents nicotine-induced mitochondrial fission, enhances cell viability, and inhibits Drp1 phosphorylation.http://www.sciencedirect.com/science/article/pii/S0147651324014143SmokingNicotinePeriodontitisHuman periodontal ligament cellsApoptosisC‑Jun N‑terminal kinase |
| spellingShingle | Leihua Cui Meiqiao Chen Yihong Jin Huining Wang Yubo Hou Mdivi-1 alleviates nicotine-induced human periodontal ligament cells injury by inhibiting mitochondrial fission and dysfunction through the JNK/Drp1 pathway Ecotoxicology and Environmental Safety Smoking Nicotine Periodontitis Human periodontal ligament cells Apoptosis C‑Jun N‑terminal kinase |
| title | Mdivi-1 alleviates nicotine-induced human periodontal ligament cells injury by inhibiting mitochondrial fission and dysfunction through the JNK/Drp1 pathway |
| title_full | Mdivi-1 alleviates nicotine-induced human periodontal ligament cells injury by inhibiting mitochondrial fission and dysfunction through the JNK/Drp1 pathway |
| title_fullStr | Mdivi-1 alleviates nicotine-induced human periodontal ligament cells injury by inhibiting mitochondrial fission and dysfunction through the JNK/Drp1 pathway |
| title_full_unstemmed | Mdivi-1 alleviates nicotine-induced human periodontal ligament cells injury by inhibiting mitochondrial fission and dysfunction through the JNK/Drp1 pathway |
| title_short | Mdivi-1 alleviates nicotine-induced human periodontal ligament cells injury by inhibiting mitochondrial fission and dysfunction through the JNK/Drp1 pathway |
| title_sort | mdivi 1 alleviates nicotine induced human periodontal ligament cells injury by inhibiting mitochondrial fission and dysfunction through the jnk drp1 pathway |
| topic | Smoking Nicotine Periodontitis Human periodontal ligament cells Apoptosis C‑Jun N‑terminal kinase |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324014143 |
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