Oxidative Stress-induced Autophagy Compromises Stem Cell Viability

0557962 - BC 2023 RIV US eng J - Článek v odborném periodiku
Prakash, R. - Fauzia, Eram - Siddiqui, A. - Yadav, S. - Kumari, N. - Shams, M. - Naeem, A. - Praharaj, P. - Khan, M. - Bhutia, S. - Janowski, M. - Boltze, J. - Raza, S.
Oxidative Stress-induced Autophagy Compromises Stem Cell Viability.
Stem Cells. Roč. 40, č. 5 (2022), s. 468-478. ISSN 1066-5099. E-ISSN 1549-4918
Institucionální podpora: RVO:60077344
Klíčová slova: oxygen * activation * pathway * kinase * oxygen-glucose deprivation * human dental pulp stem cell * human mesenchymal stem cell * autophagy * o-2 (-) * h2o2 * Ambra1 * Beclin1
Obor OECD: Cell biology
Impakt faktor: 5.2, rok: 2022
Způsob publikování: Omezený přístup
https://academic.oup.com/stmcls/article/40/5/468/6549743?login=true

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 O-2(center dot-) 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. O-2(center dot-) 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 O-2(center dot-) 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.
Trvalý link: https://hdl.handle.net/11104/0340205