Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases
Abstract Background Smoking, alcohol abuse, and hypertension are – among others, potential risk factors for cardiovascular diseases. These risk factors generate oxidative stress and cause oxidative stress-induced DNA damage, resulting in cellular senescence and senescence-associated secretory phenot...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Journal of Inflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12950-023-00366-7 |
| _version_ | 1797453875271172096 |
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| author | Huakang Zhou Dilaware Khan Sajid Muhammad Hussain Norbert Gerdes Carsten Hagenbeck Majeed Rana Jan Frederick Cornelius Sajjad Muhammad |
| author_facet | Huakang Zhou Dilaware Khan Sajid Muhammad Hussain Norbert Gerdes Carsten Hagenbeck Majeed Rana Jan Frederick Cornelius Sajjad Muhammad |
| author_sort | Huakang Zhou |
| collection | DOAJ |
| description | Abstract Background Smoking, alcohol abuse, and hypertension are – among others, potential risk factors for cardiovascular diseases. These risk factors generate oxidative stress and cause oxidative stress-induced DNA damage, resulting in cellular senescence and senescence-associated secretory phenotype (SASP). The SASP factors in feed-forward response exacerbate inflammation and cause tissue remodeling, resulting in atherosclerotic plaque formation and rupture. Results Colchicine inhibited ROS generation and mitigated oxidative stress-induced DNA damage. It dampened oxidative stress-induced endothelial cell senescence and improved the expression of DNA repair protein KU80 and aging marker Lamin B1. The drug attenuated the expression of senescence marker P21 at mRNA and protein levels. The pathway analysis showed that colchicine inhibited NF-κB and MAPKs pathways and subdued mTOR activation. Colchicine also attenuated mRNA expression of interleukin (IL)-1β, IL-6, IL-8, MCP-1, ICAM-1, and E-selectin. Furthermore, colchicine reduced the mRNA and protein expression of matrix metalloproteinase (MMP-2). Conclusion In summary, colchicine blocked oxidative stress-induced senescence and SASP by inhibiting the activation of NF-κB and MAPKs pathways. Graphical Abstract |
| first_indexed | 2024-03-09T15:29:11Z |
| format | Article |
| id | doaj.art-4ea19ca5a96f4f8fb221ce5aa7ab69d5 |
| institution | Directory Open Access Journal |
| issn | 1476-9255 |
| language | English |
| last_indexed | 2024-03-09T15:29:11Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Inflammation |
| spelling | doaj.art-4ea19ca5a96f4f8fb221ce5aa7ab69d52023-11-26T12:20:48ZengBMCJournal of Inflammation1476-92552023-11-0120111410.1186/s12950-023-00366-7Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseasesHuakang Zhou0Dilaware Khan1Sajid Muhammad Hussain2Norbert Gerdes3Carsten Hagenbeck4Majeed Rana5Jan Frederick Cornelius6Sajjad Muhammad7Department of Neurosurgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine- Universität DüsseldorfDepartment of Neurosurgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine- Universität DüsseldorfCologne Center for Genomics (CCG), University of CologneDivision of Cardiology, Pulmonology and Vascular Medicine, Medical Faculty and University Hospital, Heinrich-Heine-University DüsseldorfClinic for Gynecology and Obstetrics, Medical Faculty, Heinrich-Heine University DüsseldorfDepartment of Oral-, Maxillofacial and Facial Plastic Surgery, University Hospital DüsseldorfDepartment of Neurosurgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine- Universität DüsseldorfDepartment of Neurosurgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine- Universität DüsseldorfAbstract Background Smoking, alcohol abuse, and hypertension are – among others, potential risk factors for cardiovascular diseases. These risk factors generate oxidative stress and cause oxidative stress-induced DNA damage, resulting in cellular senescence and senescence-associated secretory phenotype (SASP). The SASP factors in feed-forward response exacerbate inflammation and cause tissue remodeling, resulting in atherosclerotic plaque formation and rupture. Results Colchicine inhibited ROS generation and mitigated oxidative stress-induced DNA damage. It dampened oxidative stress-induced endothelial cell senescence and improved the expression of DNA repair protein KU80 and aging marker Lamin B1. The drug attenuated the expression of senescence marker P21 at mRNA and protein levels. The pathway analysis showed that colchicine inhibited NF-κB and MAPKs pathways and subdued mTOR activation. Colchicine also attenuated mRNA expression of interleukin (IL)-1β, IL-6, IL-8, MCP-1, ICAM-1, and E-selectin. Furthermore, colchicine reduced the mRNA and protein expression of matrix metalloproteinase (MMP-2). Conclusion In summary, colchicine blocked oxidative stress-induced senescence and SASP by inhibiting the activation of NF-κB and MAPKs pathways. Graphical Abstracthttps://doi.org/10.1186/s12950-023-00366-7Oxidative stressEndothelial cellsCellular senescenceInflammationColchicineNFκ-B |
| spellingShingle | Huakang Zhou Dilaware Khan Sajid Muhammad Hussain Norbert Gerdes Carsten Hagenbeck Majeed Rana Jan Frederick Cornelius Sajjad Muhammad Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases Journal of Inflammation Oxidative stress Endothelial cells Cellular senescence Inflammation Colchicine NFκ-B |
| title | Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases |
| title_full | Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases |
| title_fullStr | Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases |
| title_full_unstemmed | Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases |
| title_short | Colchicine prevents oxidative stress-induced endothelial cell senescence via blocking NF-κB and MAPKs: implications in vascular diseases |
| title_sort | colchicine prevents oxidative stress induced endothelial cell senescence via blocking nf κb and mapks implications in vascular diseases |
| topic | Oxidative stress Endothelial cells Cellular senescence Inflammation Colchicine NFκ-B |
| url | https://doi.org/10.1186/s12950-023-00366-7 |
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