Oxidative Stress-induced Autophagy Compromises Stem Cell Viability
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
35294968
DOI
10.1093/stmcls/sxac018
PII: 6549743
Knihovny.cz E-resources
- Keywords
- Ambra1, Beclin1, H2O2, O2•−, autophagy, human dental pulp stem cell, human mesenchymal stem cell, oxygen-glucose deprivation,
- MeSH
- Adaptor Proteins, Signal Transducing metabolism MeSH
- Apoptosis MeSH
- Autophagy * MeSH
- Beclin-1 metabolism pharmacology MeSH
- Glucose metabolism MeSH
- Stem Cells metabolism MeSH
- Oxygen pharmacology MeSH
- Humans MeSH
- Oxidative Stress MeSH
- Hydrogen Peroxide * pharmacology MeSH
- Reactive Oxygen Species metabolism MeSH
- Cell Survival MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Adaptor Proteins, Signal Transducing MeSH
- AMBRA1 protein, human MeSH Browser
- Beclin-1 MeSH
- Glucose MeSH
- Oxygen MeSH
- Hydrogen Peroxide * MeSH
- Reactive Oxygen Species MeSH
Stem cell therapies have emerged as a promising treatment strategy for various diseases characterized by ischemic injury such as ischemic stroke. Cell survival after transplantation remains a critical issue. We investigated the impact of oxidative stress, being typically present in ischemically challenged tissue, on human dental pulp stem cells (hDPSC) and human mesenchymal stem cells (hMSC). We used oxygen-glucose deprivation (OGD) to induce oxidative stress in hDPSC and hMSC. OGD-induced generation of O2•- or H2O2 enhanced autophagy by inducing the expression of activating molecule in BECN1-regulated autophagy protein 1 (Ambra1) and Beclin1 in both cell types. However, hDPSC and hMSC pre-conditioning using reactive oxygen species (ROS) scavengers significantly repressed the expression of Ambra1 and Beclin1 and inactivated autophagy. O2•- or H2O2 acted upstream of autophagy, and the mechanism was unidirectional. Furthermore, our findings revealed ROS-p38-Erk1/2 involvement. Pre-treatment with selective inhibitors of p38 and Erk1/2 pathways (SB202190 and PD98059) reversed OGD effects on the expression of Ambra1 and Beclin1, suggesting that these pathways induced oxidative stress-mediated autophagy. SIRT3 depletion was found to be associated with increased oxidative stress and activation of p38 and Erk1/2 MAPKs pathways. Global ROS inhibition by NAC or a combination of polyethylene glycol-superoxide dismutase (PEG-SOD) and polyethylene glycol-catalase (PEG-catalase) further confirmed that O2•- or H2O2 or a combination of both impacts stems cell viability by inducing autophagy. Furthermore, autophagy inhibition by 3-methyladenine (3-MA) significantly improved hDPSC viability. These findings contribute to a better understanding of post-transplantation hDPSC and hMSC death and may deduce strategies to minimize therapeutic cell loss under oxidative stress.
Department of Life Science National Institute of Technology Rourkela Odisha India
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