دورية أكاديمية
mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial Cells.
| العنوان: | mTOR Inhibitor Rapalink-1 Prevents Ethanol-Induced Senescence in Endothelial Cells. |
|---|---|
| المؤلفون: | Zhou, Huakang1 (AUTHOR) sajjad.muhammad@med.uni-duesseldorf.de, Li, Xuanchen1 (AUTHOR), Rana, Majeed2 (AUTHOR), Cornelius, Jan Frederick1 (AUTHOR), Khan, Dilaware1 (AUTHOR) dilaware.khan@med.uni-duesseldorf.de, Muhammad, Sajjad1,3,4 (AUTHOR) |
| المصدر: | Cells (2073-4409). Nov2023, Vol. 12 Issue 22, p2609. 13p. |
| مصطلحات موضوعية: | *ENDOTHELIAL cells, *MTOR inhibitors, *GENE expression, *MTOR protein, *CARDIOVASCULAR diseases risk factors, *DNA damage |
| مستخلص: | 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. [ABSTRACT FROM AUTHOR] |
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