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Oxidative stress-induced autophagy compromises stem cell viability
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Prakash, Ravi, Fauzia, Eram, Siddiqui, Abu Junaid, Yadav, Santosh Kumar, Kumari, Neha, Shams, Mohammad Tayyab, Naeem, Abdul, Praharaj, Prakash P., Khan, Mohsin Ali, Bhutia, Sujit Kumar, Janowski, Miroslaw, Boltze, Johannes and Raza, Syed Shadab (2022) Oxidative stress-induced autophagy compromises stem cell viability. Stem Cells, 40 (5). pp. 468-478. doi:10.1093/stmcls/sxac018 ISSN 1066-5099.
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Official URL: http://dx.doi.org/10.1093/stmcls/sxac018
Abstract
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 (hDPSC) and mesenchymal stem cell (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. Further, 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. Further, 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 inform strategies to minimize therapeutic cell loss under oxidative stress.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QH Natural history Q Science > QP Physiology R Medicine > RB Pathology |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
| Library of Congress Subject Headings (LCSH): | Mesenchymal stem cells , Stem cells -- Transplantation , Adult stem cells, Cytology , Oxidative stress , Cell death, Active oxygen in the body | ||||||||
| Journal or Publication Title: | Stem Cells | ||||||||
| Publisher: | Oxford University Press | ||||||||
| ISSN: | 1066-5099 | ||||||||
| Official Date: | May 2022 | ||||||||
| Dates: |
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| Volume: | 40 | ||||||||
| Number: | 5 | ||||||||
| Page Range: | pp. 468-478 | ||||||||
| DOI: | 10.1093/stmcls/sxac018 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Reuse Statement (publisher, data, author rights): | This is a pre-copyedited, author-produced version of an article accepted for publication in Stem Cells following peer review. The version of record Ravi Prakash, Eram Fauzia, Abu Junaid Siddiqui, Santosh Kumar Yadav, Neha Kumari, Mohammad Tayyab Shams, Abdul Naeem, Prakash P Praharaj, Mohsin Ali Khan, Sujit Kumar Bhutia, Miroslaw Janowski, Johannes Boltze, Syed Shadab Raza, Oxidative stress-induced autophagy compromises stem cell viability, Stem Cells, 2022;, sxac018, is available online at: https://doi.org/10.1093/stmcls/sxac018 | ||||||||
| Access rights to Published version: | Restricted or Subscription Access | ||||||||
| Date of first compliant deposit: | 18 March 2022 | ||||||||
| Date of first compliant Open Access: | 16 March 2023 | ||||||||
| RIOXX Funder/Project Grant: |
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