Wang Qi,Zhao Ke,Gao Yameng,Li Xin,Wu Yunqiang,Zhu Yaxin,Lyu Zhichun,Sun Huiying,Gao Huiying,Xiang Shensi,Li Changyan.Effects of ionizing radiation on mitochondrial function of mouse hematopoietic stem and progenitor cells[J].Chinese Journal of Radiological Medicine and Protection,2022,42(5):321-327
Effects of ionizing radiation on mitochondrial function of mouse hematopoietic stem and progenitor cells
Received:February 22, 2022  
DOI:10.3760/cma.j.cn112271-20220222-00064
KeyWords:Hematopoietic stem and progenitor cells  Mitochondria  Ionizing radiation
FundProject:国家自然科学基金面上项目(81770108);蛋白质组国家重点实验室自主课题(SKLP-K201802)
Author NameAffiliationE-mail
Wang Qi School of Basic Medicine, Auhui Medical University, Hefei 230032, China  
Zhao Ke Beijing Institute of Lifeomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China  
Gao Yameng School of Basic Medicine, Auhui Medical University, Hefei 230032, China  
Li Xin The Fifth Medical Center, General Hospital of PLA, Beijing 100071, China  
Wu Yunqiang Beijing Institute of Lifeomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China  
Zhu Yaxin School of Life Sciences, Hebei University, Baoding 071028, China  
Lyu Zhichun Beijing Institute of Lifeomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China  
Sun Huiying Beijing Institute of Lifeomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China  
Gao Huiying Beijing Institute of Lifeomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China  
Xiang Shensi Beijing Institute of Lifeomics, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China  
Li Changyan School of Basic Medicine, Auhui Medical University, Hefei 230032, China fmmli@163.com 
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Abstract::
      Objective To study the effect of different doses of 60Co γ-ray ionizing radiation on mitochondrial function in mouse hematopoietic stem and progenitor cells (HSPCs).Methods C57BL/6 mice were divided into control group, 1 Gy irradiation group and 4.5 Gy irradiation group. The mitochondrial functions were detected at 12 h and 24 h after irradiation, including ROS level, membrane potential, mitochondrial structure, and mitochondrial stress. Bone marrow c-Kit+ cells received a single 15 Gy irradiation in vitro, after 24 h, mitochondrial function was detected.Results It was found that mice leukocytes (t=12.41, 18.31, 16.48, 14.16, 19.08, 20.25, P<0.05), red blood cells (t=4.81, 6.62, P<0.05) and platelets (t=4.33, 6.68, P<0.05) were significantly reduced. The numbers of bone marrow colony formation unit (t=16.27, 55.66, 17.06, 43.75, P<0.05), and HSPCs (t=5.16, 11.55, P<0.05) were decreased dose-dependently post-irradiation. Under 1 Gy irradiation, the mitochondrial function and mitochondrial basal metabolic index of HSPCs (t= 7.36, 3.68, 4.58, 3.15, 3.15, P<0.05) were enhanced at 24 h post-irradiation. Under 4.5 Gy irradiation, mitochondrial number, mitochondrial membrane potential (t=12.29, 10.46, P<0.05), maximal respiration and spare respiratory capacity were decreased (t=7.81, 5.78, 6.70, 5.83, P<0.05), ROS level was increased (t=4.63, 4.12, P<0.05). The basal respiration and oxidative phosphorylated ATP production were reduced at 12 h after irradiation (t=8.48, 3.80, P<0.05); and the proton leakage was increased (t=6.57, P<0.05) and coupling efficiency was reduced (t=11.43, P<0.05) at 24 h after irradiation. In cultured c-Kit+ cells, the level of ROS (t=11.30, P<0.05) and the maximum respiration and spare respiratory capacity were increased (t=4.25, 3.44, P<0.05) while the mitochondrial membrane potential was decreased (t=34.92, P<0.05) significantly.Conclusions A method for systematically assessing mitochondrial function in HSPCs was established, and the effect of ionizing radiation on mitochondrial function of HSPCs was clarified, laying a foundation for further revealing the mechanism of ionizing radiation-induced mitochondrial damage in HSPCs.
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