期刊
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
卷 2020, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2020/8291413
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资金
- National Natural Science Foundation of China [31960191, 81660363]
- Science and Technology Innovation Leading Academics of National High-level Personnel of Special Support Program [GKFZ-2018-29]
- Guizhou High-Level Innovative Talent Support Program [QKH-RC-20154028]
- Science and Technology Foundation of Guizhou [QKH-2017-1422]
Aging is an important risk factor in the occurrence of many chronic diseases. Senescence and exhaustion of adult stem cells are considered as a hallmark of aging in organisms. In this study, a senescent human amniotic mesenchymal stem cell (hAMSC) model subjected to oxidative stress was establishedin vitrousing hydrogen peroxide. We investigated the effects of ganoderic acid D (GA-D), a natural triterpenoid compound produced fromGanoderma lucidum, on hAMSC senescence. GA-D significantly inhibited beta-galactosidase (a senescence-associated marker) formation, in a dose-dependent manner, with doses ranging from 0.1 mu M to 10 mu M, without inducing cytotoxic side-effects. Furthermore, GA-D markedly inhibited the generation of reactive oxygen species (ROS) and the expression of p21 and p16 proteins, relieved the cell cycle arrest, and enhanced telomerase activity in senescent hAMSCs. Furthermore, GA-D upregulated the expression of phosphorylated protein kinase R- (PKR-) like endoplasmic reticulum kinase (PERK), peroxidase III (PRDX3), and nuclear factor-erythroid 2-related factor (NRF2) and promoted intranuclear transfer of NRF2 in senescent cells. The PERK inhibitor GSK2656157 and/or the NRF2 inhibitor ML385 suppressed the PERK/NRF2 signaling, which was activated by GA-D. They induced a rebound for the generation of ROS and beta-galactosidase-positive cells and attenuated the differentiation capacity. These findings suggest that GA-D retards hAMSC senescence through activation of the PERK/NRF2 signaling pathway and may be a promising candidate for the discovery of antiaging agents.
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