mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial Cells
The cardiovascular risk factors, including smoking, ethanol, and oxidative stress, can induce cellular senescence. The senescent cells increase the expression and release of pro-inflammatory molecules and matrix metalloproteinase (MMPs). These pro-inflammatory molecules and MMPs promote the infiltra...
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MDPI AG
2023-11-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/22/2609 |
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| author | Huakang Zhou Xuanchen Li Majeed Rana Jan Frederick Cornelius Dilaware Khan Sajjad Muhammad |
| author_facet | Huakang Zhou Xuanchen Li Majeed Rana Jan Frederick Cornelius Dilaware Khan Sajjad Muhammad |
| author_sort | Huakang Zhou |
| collection | DOAJ |
| description | The cardiovascular risk factors, including smoking, ethanol, and oxidative stress, can induce cellular senescence. The senescent cells increase the expression and release of pro-inflammatory molecules and matrix metalloproteinase (MMPs). These pro-inflammatory molecules and MMPs promote the infiltration and accumulation of inflammatory cells in the vascular tissue, exacerbating vascular tissue inflammation. MMPs damage vascular tissue by degenerating the extracellular matrix. Consequently, these cellular and molecular events promote the initiation and progression of cardiovascular diseases. We used Rapalink-1, an mTOR inhibitor, to block ethanol-induced senescence. Rapalink-1 inhibited oxidative-stress-induced DNA damage and senescence in endothelial cells exposed to ethanol. It attenuated the relative protein expression of senescence marker P21 and improved the relative protein expression of DNA repair protein KU70 and aging marker Lamin B1. It inhibited the activation of NF-κB, MAPKs (P38 and ERK), and mTOR pathway proteins (mTOR, 4EBP-1, and S6). Moreover, Rapalink-1 suppressed ethanol-induced mRNA expression of ICAM-1, E-selectin, MCP-1, IL-8, MMP-2, and TIMP-2. Rapalink-1 also reduced the relative protein expression of MMP-2. In summary, Rapalink-1 prevented senescence, inhibited pro-inflammatory pathway activation, and ameliorated pro-inflammatory molecule expression and MMP-2. |
| first_indexed | 2024-03-09T16:55:58Z |
| format | Article |
| id | doaj.art-a36474bc46794e6fb8f1f1069cd08257 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T16:55:58Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-a36474bc46794e6fb8f1f1069cd082572023-11-24T14:35:15ZengMDPI AGCells2073-44092023-11-011222260910.3390/cells12222609mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial CellsHuakang Zhou0Xuanchen Li1Majeed Rana2Jan Frederick Cornelius3Dilaware Khan4Sajjad Muhammad5Department of Neurosurgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, GermanyDepartment of Neurosurgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, GermanyDepartment of Oral and Maxillofacial Surgery, Medical Faculty, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, GermanyDepartment of Neurosurgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, GermanyDepartment of Neurosurgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, GermanyDepartment of Neurosurgery, Medical Faculty, University Hospital Düsseldorf, Heinrich-Heine-University, Moorenstrasse 5, 40225 Düsseldorf, GermanyThe cardiovascular risk factors, including smoking, ethanol, and oxidative stress, can induce cellular senescence. The senescent cells increase the expression and release of pro-inflammatory molecules and matrix metalloproteinase (MMPs). These pro-inflammatory molecules and MMPs promote the infiltration and accumulation of inflammatory cells in the vascular tissue, exacerbating vascular tissue inflammation. MMPs damage vascular tissue by degenerating the extracellular matrix. Consequently, these cellular and molecular events promote the initiation and progression of cardiovascular diseases. We used Rapalink-1, an mTOR inhibitor, to block ethanol-induced senescence. Rapalink-1 inhibited oxidative-stress-induced DNA damage and senescence in endothelial cells exposed to ethanol. It attenuated the relative protein expression of senescence marker P21 and improved the relative protein expression of DNA repair protein KU70 and aging marker Lamin B1. It inhibited the activation of NF-κB, MAPKs (P38 and ERK), and mTOR pathway proteins (mTOR, 4EBP-1, and S6). Moreover, Rapalink-1 suppressed ethanol-induced mRNA expression of ICAM-1, E-selectin, MCP-1, IL-8, MMP-2, and TIMP-2. Rapalink-1 also reduced the relative protein expression of MMP-2. In summary, Rapalink-1 prevented senescence, inhibited pro-inflammatory pathway activation, and ameliorated pro-inflammatory molecule expression and MMP-2.https://www.mdpi.com/2073-4409/12/22/2609ethanolendothelial cellssenescenceSASPRapalink-1NFκ-B |
| spellingShingle | Huakang Zhou Xuanchen Li Majeed Rana Jan Frederick Cornelius Dilaware Khan Sajjad Muhammad mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial Cells Cells ethanol endothelial cells senescence SASP Rapalink-1 NFκ-B |
| title | mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial Cells |
| title_full | mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial Cells |
| title_fullStr | mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial Cells |
| title_full_unstemmed | mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial Cells |
| title_short | mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial Cells |
| title_sort | mtor inhibitor rapalink 1 prevents ethanol induced senescence in endothelial cells |
| topic | ethanol endothelial cells senescence SASP Rapalink-1 NFκ-B |
| url | https://www.mdpi.com/2073-4409/12/22/2609 |
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