Ganoderic Acid D Protects Human Amniotic Mesenchymal Stem Cells against Oxidative Stress-Induced Senescence through the PERKNRF2 Signaling Pathway
Joint Authors
Xu, Yan
Yuan, Huan
Luo, Yi
Zhao, Yu-Jie
Xiao, Jian-Hui
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-18, 18 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-07-28
Country of Publication
Egypt
No. of Pages
18
Main Subjects
Abstract EN
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 established in vitro using hydrogen peroxide.
We investigated the effects of ganoderic acid D (GA-D), a natural triterpenoid compound produced from Ganoderma lucidum, on hAMSC senescence.
GA-D significantly inhibited β-galactosidase (a senescence-associated marker) formation, in a dose-dependent manner, with doses ranging from 0.1 μM to 10 μM, 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 β-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.
American Psychological Association (APA)
Xu, Yan& Yuan, Huan& Luo, Yi& Zhao, Yu-Jie& Xiao, Jian-Hui. 2020. Ganoderic Acid D Protects Human Amniotic Mesenchymal Stem Cells against Oxidative Stress-Induced Senescence through the PERKNRF2 Signaling Pathway. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-18.
https://search.emarefa.net/detail/BIM-1205565
Modern Language Association (MLA)
Xu, Yan…[et al.]. Ganoderic Acid D Protects Human Amniotic Mesenchymal Stem Cells against Oxidative Stress-Induced Senescence through the PERKNRF2 Signaling Pathway. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-18.
https://search.emarefa.net/detail/BIM-1205565
American Medical Association (AMA)
Xu, Yan& Yuan, Huan& Luo, Yi& Zhao, Yu-Jie& Xiao, Jian-Hui. Ganoderic Acid D Protects Human Amniotic Mesenchymal Stem Cells against Oxidative Stress-Induced Senescence through the PERKNRF2 Signaling Pathway. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-18.
https://search.emarefa.net/detail/BIM-1205565
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1205565