Quan Yi, Yu Xiaofang
Institute of Nuclear Physics and Chemistry, China Academy of Engineering Physics, Mianyang 621900, China.
Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Suzhou 215000, China.
Biology (Basel). 2024 Jul 16;13(7):525. doi: 10.3390/biology13070525.
Bone is a major tissue for uranium deposition in human body. Considering mesenchymal stem cells (MSCs) play a vital role in bone formation and injury recovery, studying the mechanism of MSCs responding to uranium poisoning can benefit the understanding of bone damage and repair after uranium exposure. Cellular structural alterations were analyzed via transmission electron microscopy (TEM). Changes in cellular behaviors were assessed through cellular viability, apoptosis, and the production of DNA double-strand breaks (DSBs). In addition, the influence of gap junctional intercellular communication (GJIC) on uranium toxicity was assessed. The disruption of MSCs was elevated with the increase in uranyl nitrate concentration, as shown by TEM micrograph. This was verified by the results of cellular viability and DSB production. Interestingly, the results of apoptosis assay indicated significant apoptosis occurred, which was accompanied with an obvious disruption of cellular membranes. Furthermore, closely contacted cell confluence groups exhibited resistant to uranium poisoning in contrast to sparse growth groups, which can be eliminated with the pretreatment of a GJIC inhibitor in the close connection group. To verify the association between GJIC and cytotoxic effects of uranyl nitrate, GJIC function was evaluated by wound healing and cellular migration. The results showed an inhibition of the healing ratio and migration ability induced by the exposure of uranyl nitrate. The low transfer efficiency of the dye coupling experiment and depressed expression of gap functional protein connexins confirmed the impairment of GJIC function. These results suggest that uranium toxicity is involved with GJIC dysfunction.
骨骼是人体中铀沉积的主要组织。鉴于间充质干细胞（MSCs）在骨形成和损伤恢复中起着至关重要的作用，研究MSCs对铀中毒的反应机制有助于理解铀暴露后的骨损伤和修复。通过透射电子显微镜（TEM）分析细胞结构改变。通过细胞活力、凋亡以及DNA双链断裂（DSBs）的产生来评估细胞行为的变化。此外，评估了间隙连接细胞间通讯（GJIC）对铀毒性的影响。如TEM显微照片所示，随着硝酸铀酰浓度的增加，MSCs的破坏加剧。这通过细胞活力和DSB产生的结果得到证实。有趣的是，凋亡检测结果表明发生了显著的凋亡，同时伴有细胞膜的明显破坏。此外，与稀疏生长组相比，紧密接触的细胞汇合组对铀中毒具有抗性，而在紧密连接组中用GJIC抑制剂预处理可消除这种抗性。为了验证GJIC与硝酸铀酰细胞毒性作用之间的关联，通过伤口愈合和细胞迁移评估GJIC功能。结果显示硝酸铀酰暴露诱导的愈合率和迁移能力受到抑制。染料偶联实验的低转移效率和间隙功能蛋白连接蛋白的表达降低证实了GJIC功能受损。这些结果表明铀毒性与GJIC功能障碍有关。
