Synergistic Protection of N-Acetylcysteine and Ascorbic Acid 2-Phosphate on Human Mesenchymal Stem cells Against Mitoptosis, Necroptosis and Apoptosis

被引:62
作者
Li, Chia-Jung [1 ]
Sun, Li-Yi [2 ]
Pang, Cheng-Yoong [1 ,2 ]
机构
[1] Tzu Chi Univ, Inst Med Sci, Hualien, Taiwan
[2] Buddhist Tzu Chi Gen Hosp, Dept Med Res, Hualien, Taiwan
来源
SCIENTIFIC REPORTS | 2015年 / 5卷
关键词
CASPASE-INDEPENDENT NECROPTOSIS; PEROXIDE-INDUCED APOPTOSIS; BONE-MARROW; POLY(ADP-RIBOSE) POLYMERASE-1; OSTEOGENIC DIFFERENTIATION; OXIDATIVE STRESS; NECROSIS; DEATH; PROLIFERATION; MITOCHONDRIA;
D O I
10.1038/srep09819
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Human mesenchymal stem cells (hMSCs) contribute to ischemic tissue repair, regeneration, and possess ability to self-renew. However, poor viability of transplanted hMSCs within ischemic tissues has limited its therapeutic efficiency. Therefore, it is urgent to explore new method to improve the viability of the grafted cells. By using a systematic analysis, we reveal the mechanism of synergistic protection of N-acetylcysteine (NAC) and ascorbic acid 2-phosphate (AAP) on hMSCs that were under H2O2-induced oxidative stress. The combined treatment of NAC and AAP (NAC/AAP) reduces reactive oxygen species (ROS) generation, stabilizes mitochondrial membrane potential and decreases mitochondrial fission/fragmentation due to oxidative stress. Mitochondrial fission/fragmentation is a major prologue of mitoptosis. NAC/AAP prevents apoptotic cell death via decreasing the activation of BAX, increasing the expression of BCL2, and reducing cytochrome c release from mitochondria that might lead to the activation of caspase cascade. Stabilization of mitochondria also prevents the release of AIF, and its nuclear translocation which may activate necroptosis via H2AX pathway. The decreasing of mitoptosis is further studied by MicroP image analysis, and is associated with decreased activation of Drp1. In conclusion, NAC/AAP protects mitochondria from H2O2-induced oxidative stress and rescues hMSCs from mitoptosis, necroptosis and apoptosis.
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页数:12
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