| Yuan Yayi,Bai Jiamei,Tian Lianchen,et al.Effects of uranyl nitrate on mitochondrial structure and function[J].Chinese Journal of Radiological Medicine and Protection,2025,45(12):1237-1244 |
| Effects of uranyl nitrate on mitochondrial structure and function |
| Received:December 13, 2024 |
| DOI：10.3760/cma.j.cn112271-20241213-00476 |
| KeyWords:Uranium Nephrotoxicity Mitochondrial dynamics Molecular mechanism |
| FundProject:国家自然科学基金联合基金(U216720073) |
| Author Name | Affiliation | E-mail | | Yuan Yayi | Department of Radiology and Environmental Medicine, China Institute for Radiation Protection, Taiyuan 030006, China
College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430071, China | | | Bai Jiamei | Department of Radiology and Environmental Medicine, China Institute for Radiation Protection, Taiyuan 030006, China | | | Tian Lianchen | Department of Radiology and Environmental Medicine, China Institute for Radiation Protection, Taiyuan 030006, China | | | Zuo Yahui | Department of Radiology and Environmental Medicine, China Institute for Radiation Protection, Taiyuan 030006, China | | | Wang Xiaomei | School for Radiological and Interdisciplinary Sciences(RAD-X), Soochow University, Suzhou 215009, China | | | Dong Juancong | Department of Radiology and Environmental Medicine, China Institute for Radiation Protection, Taiyuan 030006, China | | | Cheng Jiao | Department of Radiology and Environmental Medicine, China Institute for Radiation Protection, Taiyuan 030006, China | | | Dang Xuhong | Department of Radiology and Environmental Medicine, China Institute for Radiation Protection, Taiyuan 030006, China
Collaborative Innovation Center of Radiological Medicine, Suzhou 215009, China | dangxuhong005@163.com |
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| Abstract:: |
| Objective To investigate the human renal tubular epithelial cells (HK-2 cells) to determine the effects of uranium exposure on the mitochondrial morphology, structure, and functions (e.g., oxidative stress and energy metabolism) in HK-2 cells and to explore the potential mechanisms underlying uranium-induced injury to HK-2 cells from the perspective of mitochondrial dynamics.Methods HK-2 cells were cultured using a 100 μmol/L uranyl nitrate solution for different times (0, 3, 6, 12, and 24 h). Then, changes in mitochondrial morphology and structure post-exposure were observed using a confocal laser scanning microscope. The effects of uranyl nitrate on oxidative stress levels in HK-2 cells were analyzed based on malondialdehyde (MDA) concentration, and reactive oxygen species (ROS) levels, as well as the activity of catalase (CAT) and superoxide dismutase (SOD). Meanwhile, the effects of uranyl nitrate on energy metabolism in HK-2 cells were investigated based on mitochondrial membrane potential (MMp), the enzyme activity of respiratory chain complexes Ⅳ and Ⅴ in mitochondria, and the adenosine triphosphate (ATP) content. Using Western blot (WB), the effects of uranyl nitrate exposure on the expression of mitochondrial dynamics-related proteins (Mfn1, Mfn2, Opa1, Drp1, and Fis1) were analyzed and the proteins sensitive to uranyl nitrate-induced damage were determined.Results At 3 h post-exposure, mitochondrial morphology in HK-2 cells gradually transitioned to a distinct fragmented structure. At 6 h post-exposure, the HK-2 cells exhibited significant increases in ROS and MDA concentrations (t = 89.06, 39.40, P < 0.05), distinct decreases in CAT and SOD enzyme activities (t = 14.49, 12.12, P < 0.05), and time-dependent reductions in the enzyme activities of respiratory chain complexes Ⅳ and Ⅴ in mitochondria, ATP content, and MMp (t = 2.64-31.51, P < 0.05), a decline in ATP-linked respiratory capacity, and time-dependent significant increased in the expression levels of proteins Drp1 and Fis1 (tDrp1 = 14.02-185.70, P < 0.05; tFis1 = 19.72-165.10, P < 0.05).Conclusions Mitochondrial structural damage precedes mitochondrial functional impairments, and abnormal mitochondrial dynamics might be a potential cause of the structural damage. Fission proteins Drp1 and Fis1 represent potential key targets of uranium-induced damage. These findings provide a basis for investigating the mechanisms behind uranium-induced nephrotoxicity and offer new targets for the prevention and treatment of uranium poisoning. |
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