Mitophagy is a protective response against oxidative damage in bone marrow mesenchymal stem cells
Mitophagy is a protective response against oxidative damage in bone marrow mesenchymal stem cells
复制标题
线粒体自噬是骨髓间充质干细胞针对氧化损伤的保护性反应
DOI：
10.1016/j.lfs.2019.05.027
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发表时间：
2019-07-15
期刊：
影响因子：
6.1
通讯作者：
Wang, Yun-Tao
中科院分区：
文献类型：
--
作者：
Fan, Pan;Yu, Xiao-Yu;Wang, Yun-Tao
目的：骨髓间充质干细胞（BMSCs）在椎间盘退变等临床应用中具有巨大的潜力。然而，骨髓间充质干细胞移植过程中或损伤组织中的环境应激是导致细胞毒性和骨髓间充质干细胞生存不良的灾难性因素。线粒体自噬在维持细胞稳态和抵御氧化应激方面起着至关重要的作用，因为这一过程可以通过消除导致细胞死亡的功能失调或受损的线粒体来控制线粒体的质量和数量。然而，线粒体自噬保护骨髓间充质干细胞免受严重氧化应激的确切机制在很大程度上仍然未知。主要方法：采用不同时间的H2O2处理骨髓间充质干细胞。Western blot和荧光分析通过LC3-II、p62的表达水平和线粒体形成来评估线粒体自噬反应。流式细胞术和TUNEL法检测细胞凋亡。通过将线粒体自噬抑制剂或线粒体自噬激活剂与H2O2共处理，研究线粒体自噬与细胞凋亡的相互作用及其可能的信号通路。主要发现：氧化应激在早期通过JNK快速促进线粒体自噬，但在后期减少线粒体自噬并增加细胞凋亡。此外，线粒体自噬抑制显著增强H2O2处理的细胞凋亡。意义：诱导线粒体自噬可能在骨髓间充质干细胞抗氧化应激中起关键作用。
Aims: Bone marrow mesenchymal stem cells (BMSCs) show great potential in clinical applications such as in intervertebral disc degeneration. Nevertheless, environmental stress during the BMSC transplant or in the injured tissues is a catastrophic factor that causes cell toxicity and poor survival of BMSCs. Mitophagy plays a vital role in maintaining cellular homeostasis and defending against oxidative stress because this process could control mitochondrial quality and quantity by eliminating dysfunctional or damaged mitochondria that can cause cell death. However, the accurate mechanisms of mitophagy in protecting BMSCs against the harshness of oxidative stress remain largely unknown.Main methods: BMSCs were treated with H2O2 for various time periods. Mitophagy response was evaluated through the expression levels of LC3-II, p62 and mitophagosomal formation by using Western blot and fluorescence analysis. Cell apoptosis was examined by flow cytometry and TUNEL assay. The interactions of mitophagy and apoptosis and the possible signalling pathways were investigated through the co-treatment of mitophagy inhibitor or mitophagy activator with H2O2.Key findings: Oxidative stress rapidly facilitated mitophagy through JNK at an early stage but decreased mitophagy and increased apoptosis at a late stage. Furthermore, mitophagy inhibition significantly enhanced the apoptosis in the cells treated by H2O2.Significance: Induced mitophagy may play pivotal roles in protecting cells against oxidative stress in BMSCs.