Rapamycin Protects Skin Fibroblasts from Ultraviolet B-Induced Photoaging by Suppressing the Production of Reactive Oxygen Species
| Autor: | Runjian Ren, Liang Chen, Qin Dengke, Bi Bo, Zhu Jingjing, Xinyuan Wu, Ningwen Zhu, Ping Yang, Yongzhou Lu, Guo Yu, Tianyi Liu, Chuanlong Jia, Yang Qingjian, Zhou Yiqun |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Cell cycle checkpoint Physiology DNA damage Cell Survival Ultraviolet Rays Photoaging Cell morphology lcsh:Physiology lcsh:Biochemistry 03 medical and health sciences Mice medicine Autophagy Animals lcsh:QD415-436 Rapamycin Cells Cultured Cellular Senescence Cell Proliferation chemistry.chemical_classification Sirolimus Reactive oxygen species lcsh:QP1-981 Cell growth Chemistry ROS Cell Cycle Checkpoints Fibroblasts medicine.disease Cell biology Skin Aging Mice Inbred C57BL 030104 developmental biology Female Uvb Reactive Oxygen Species Sunscreening Agents Intracellular |
| Zdroj: | Cellular Physiology and Biochemistry, Vol 46, Iss 5, Pp 1849-1860 (2018) |
| ISSN: | 1421-9778 |
| Popis: | Background/Aims: Ultraviolet B (UVB) irradiation alters multiple molecular pathways in the skin, thereby inducing skin photoaging. Murine dermal fibroblasts (MDFs) were subjected to a series of 4 sub-cytotoxic UVB doses (120 mJ/cm2), resulting in changes in cell shape, DNA damage, cell cycle arrest, extracellular matrix variations, reactive oxygen species (ROS) generation, and alterations in major intracellular antioxidant and cellular autophagy levels. Rapamycin (RAPA) is a new macrolide immunosuppressive agent that is primarily used in oncology, cardiology, and transplantation medicine and has been found to extend the lifespan of genetically heterogeneous mice. Several studies have shown that RAPA may have anti-aging effects in cells and organisms. Thus, in this study, we explored the effects and mechanisms of RAPA against the photoaging process using a well-established cellular photoaging model. Methods: We developed a stress-induced premature senescence (SIPS) model through repeated exposure of MDFs to ultraviolet B (UVB) irradiation. The cells were cultured in the absence or presence of RAPA for 48 h. Senescent phenotypes were assessed by examining cell viability, cell morphology, senescence-associated β-galactosidase (SA-β-gal) expression, cell cycle progression, intracellular ROS production, matrix metalloproteinase (MMP) synthesis and degradation, extracellular matrix (ECM) component protein expression, alterations in major intracellular antioxidant levels, and the cellular autophagy level. Results: Compared with the UVB group, pretreatment with RAPA (5 µM) significantly decreased the staining intensity and percentage of SA-β-gal-positive cells and preserved the elongated cell shape. Moreover, cells pretreated with RAPA showed inhibition of the reduction in the type I collagen content by blocking the UVB-induced upregulation of MMP expression. RAPA also decreased photoaging cell cycle arrest and downregulated p53 and p21 expression. RAPA application significantly attenuated irradiation-induced ROS release by modulating intracellular antioxidants and increasing the autophagy level. Conclusions: Our study demonstrated that RAPA elicited oxidative damage in vitro by reducing ROS accumulation in photoaged fibroblasts. The anti-aging effect can be attributed to the maintenance of normal antioxidant and cellular autophagy levels. However, determination of the definitive mechanism requires further study. |
| Databáze: | OpenAIRE |
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