Valproic acid and/or rapamycin preconditioning protects hair follicle stem cells from oxygen glucose serum deprivation-induced oxidative injury via activating Nrf2 pathway | ||
| Molecular Biology Research Communications | ||
| دوره 13، شماره 3، 2024، صفحه 103-116 اصل مقاله (1.08 M) | ||
| نوع مقاله: Original article | ||
| شناسه دیجیتال (DOI): 10.22099/mbrc.2024.49302.1922 | ||
| نویسندگان | ||
| Fatemeh Keshavarzi1؛ Mohammad Saied Salehi2؛ Sareh Pandamooz3؛ Razieh Zare1؛ Mozhdeh Zamani4؛ Zohreh Mostafavipour* 5؛ Pooneh Mokarram* 4 | ||
| 1Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran | ||
| 2Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran | ||
| 3Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran | ||
| 4Autophagy Research Center, Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran | ||
| 5Maternal-Fetal Medicine Research Center, Shiraz University of Medical Sciences, Shiraz, Iran | ||
| چکیده | ||
| Among leading causes of the ischemic stroke pathogenesis, oxidative stress strongly declines rate of stem cell engraftment at the injury site, and disables stem cell-based therapy as a key treatment for ischemia stroke. To overcome this therapeutic limitation, preconditioning has been represented a possible approach to augment the adaptation and viability of stem cells to oxidative stress. Here, we illustrated protective impacts of valproic acid (VPA) and/or rapamycin (RAPA) preconditioning unto oxygen glucose and serum deprivation (OGSD)-stimulated cell damage in hair follicle-derived stem cells (HFSCs) and surveyed the plausible inducement mechanisms. OGSD, as an in vitro cell injury model, was established and HFSCs viability was observed using MTT assay after VPA, RAPA, and VPA-RAPA preconditioning under OGSD. ROS and MDA production was assessed to reflect oxidative stress. Real-time PCR and western blotting were employed to investigate Nrf2 expression. The activity of Nrf2-related antioxidant enzymes including NQO1, GPx and GSH level were examined. VEGF and BDNF mRNA expression levels were analyzed. Our results showed that VPA and/or RAPA preconditioning ameliorated OGSD-induced decline in HFSCs viability. In addition, they considerably prohibited ROS and MDA generation in the OGSD-treated HFSCs. Furthermore, VPA and/or RAPA preconditioning stimulated Nrf2 nuclear repositioning and NQO1 and GPx activity and GSH amount, as well as expression of paracrine factors VEGF and BDNF in OGSD-treated HFSCs. Thus, the protective effects afforded by VPA and/or RAPA preconditioning, which involved Nrf2-modulated oxidant stress and regulation of VEGF and BDNF expression, display a simple strategy to augment cell-transplantation efficiency for ischemic stroke. | ||
| کلیدواژهها | ||
| Ischemic stroke؛ Oxidative stress؛ Nrf2؛ Valproic acid؛ Rapamycin؛ Hair follicle stem cell | ||
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