期刊
DRUG DESIGN DEVELOPMENT AND THERAPY
卷 13, 期 -, 页码 747-755出版社
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S179894
关键词
oxidative stress; senescence; LC3; p62; p-Rb
资金
- National Natural Science Foundation of China [81771507]
- Natural Science Foundation of Guangdong Province [2016A030313755]
- Special Fund for Economic and Technological Development of Longgang District in Shenzhen [201606031610304]
Purpose: Resveratrol (RESV; trans-3,5,4'-trihydroxystilbene) has emerged as a potential new therapeutic for age-related atherosclerotic diseases. However, the effect of RESV on cellular aging and its underlying mechanisms remain unknown. Therefore, the aim of this study was to examine whether RESV can delay cellular aging through upregulation of autophagy. Materials and methods: Human umbilical endothelial vein cells (HUVECs) were divided into four groups: the control group, and the hydrogen peroxide (H2O2) alone, H2O2 + RESV pretreatment, and H2O2 + 3-methyladenine (3-MA) + RESV pretreatment intervention groups. The cell viability was evaluated by a cell counting kit-8 assay. Superoxide dismutase (SOD) activity and intracellular reactive oxygen species (ROS) levels were tested using commercial kits. Senescence-related beta-galactosidase activities were detected by immunohistochemical staining. The expression levels of aging-related and autophagyrelated markers, including phosphorylated Rb (p-Rb), LC3, and p62, with or without RESV were measured by Western blotting. Results: Pretreatment with 10 mu M RESV increased the cell viability and SOD levels. The remarkably higher positive rate of senescence-associated beta-galactosidase and increased intracellular ROS levels in the H2O2 treatment group were reversed by treatment with 10 mu M RESV. As compared to the H2O2 treatment group, 10 mu M RESV could upregulate autophagy through the regulation of p-Rb, LC3, and p62 levels. The anti-aging effect of RESV via an autophagy regulation mechanism was further confirmed by the suppression of these effects with 3-MA treatment. Conclusion: RESV may reverse and delay the aging process of HUVECs via upregulation of autophagy and could be a candidate therapeutic for age-related atherosclerotic diseases.
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