Stem cell therapies are becoming increasingly popular solutions for neurological disorders. However, there is a lower survival rate of these cells after transplantation. Oxidative stress is linked to brain damage, and it may also impact transplanted stem cells. To better understand how transplanted cells respond to oxidative stress, the current study used H₂O₂. We briefly illustrated that exogenous H₂O₂ treatment exaggerated oxidative stress in the human dental pulp and mesenchymal stem cells. 2′,7′-Dichlorofluorescin diacetate (DCFDA), MitoSOX confirms the reactive oxygen species (ROS) involvement, which was remarkably subsided by the ROS inhibitors. The findings showed that H₂O₂ activates autophagy by enhancing pro-autophagic proteins, Beclin1 and Atg7. Increased LC3II/I expression (which co-localized with lysosomal proteins, LAMP1 and Cathepsin B) showed that H₂O₂ treatment promoted autophagolysosome formation. In the results, both Beclin1 and Atg7 were observed co-localized in mitochondria, indicating their involvement in mitophagy. The evaluation of Erk1/2 in the presence and absence of Na-Pyruvate, PEG-Catalase, and PD98059 established ROS-Erk1/2 participation in autophagy regulation. Further, these findings showed a link between apoptosis and autophagy. The results conclude that H₂O₂ acts as a stressor, promoting autophagy and mitophagy in stem cells under oxidative stress. The current study may help understand better cell survival and death approaches for transplanted cells in various neurological diseases.

Graphical abstract

The current study uses human Dental Pulp and Mesenchymal Stem cells to demonstrate the importance of H₂O₂-driven autophagy in deciding the fate of these cells in an oxidative microenvironment. To summarise, we discovered that exogenous H₂O₂ treatment causes oxidative stress. Exogenous H₂O₂ treatment also increased ROS production, especially intracellular H₂O₂. H₂O₂ stimulated the ErK1/2 signaling pathway and autophagy. Erk1/2 was found to cause autophagy. Further, the function of mitophagy appeared to be an important factor in the H₂O₂-induced regulation of these two human stem cell types. In a nutshell, by engaging in autophagy nucleation, maturation, and terminal phase proteins, we elucidated the participation of autophagy in cell dysfunction and death.

中文翻译：

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氧化应激通过 Erk1/2 信号通路增强自噬介导的干细胞死亡——对神经移植的意义

干细胞疗法正成为越来越流行的神经系统疾病解决方案。然而，移植后这些细胞的存活率较低。氧化应激与脑损伤有关，它也可能影响移植的干细胞。为了更好地了解移植细胞对氧化应激的反应，目前的研究使用了 H ₂ O ₂。我们简要说明了外源性 H ₂ O ₂处理夸大了人牙髓和间充质干细胞中的氧化应激。2',7'-二氯荧光素二乙酸酯 (DCFDA)，MitoSOX 证实了活性氧 (ROS) 的参与，这被 ROS 抑制剂显着消退。研究结果表明，H ₂ O ₂通过增强前自噬蛋白 Beclin1 和 Atg7 来激活自噬。增加的 LC3II/I 表达（与溶酶体蛋白、LAMP1 和组织蛋白酶 B 共定位）表明 H ₂ O ₂处理促进了自噬溶酶体的形成。结果显示，Beclin1 和 Atg7 均位于线粒体中，表明它们参与了线粒体自噬。在存在和不存在 Na-Pyruvate、PEG-过氧化氢酶和 PD98059 的情况下对 Erk1/2 的评估确定了 ROS-Erk1/2 参与自噬调节。此外，这些发现表明细胞凋亡和自噬之间存在联系。结果得出结论，H ₂ O ₂作为应激源，在氧化应激下促进干细胞的自噬和线粒体自噬。目前的研究可能有助于了解移植细胞在各种神经系统疾病中更好的细胞存活和死亡方法。

图形概要

目前的研究使用人类牙髓和间充质干细胞来证明 H ₂ O ₂驱动的自噬在决定这些细胞在氧化微环境中的命运中的重要性。总而言之，我们发现外源 H ₂ O ₂处理会导致氧化应激。外源 H ₂ O ₂处理也增加了 ROS 的产生，尤其是细胞内的 H ₂ O ₂。H ₂ O ₂刺激ErK1/2信号通路和自噬。发现 Erk1/2 引起自噬。此外，线粒体自噬的功能似乎是 H ₂ O _{2中的一个重要因素。}-这两种人类干细胞类型的诱导调节。简而言之，通过参与自噬成核、成熟和终末期蛋白，我们阐明了自噬在细胞功能障碍和死亡中的参与。