Varlamova Elena G, Baryshev Alexey S, Gudkov Sergey V, Babenko Valentina A, Plotnikov Egor Y, Turovsky Egor A
Institute of Cell Biophysics of the Russian Academy of Sciences, Federal Research Center "Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences", 142290 Pushchino, Russia.
Prokhorov General Physics Institute of the Russian Academy of Sciences, 38 Vavilove St., 119991 Moscow, Russia.
Int J Mol Sci. 2023 Sep 19;24(18):14305. doi: 10.3390/ijms241814305.
Most of the works aimed at studying the cytoprotective properties of nanocerium are usually focused on the mechanisms of regulation of the redox status in cells while the complex effects of nanocerium on calcium homeostasis, the expression of pro-apoptotic and protective proteins are generally overlooked. There is a problem of a strong dependence of the effects of cerium oxide nanoparticles on their size, method of preparation and origin, which significantly limits their use in medicine. In this study, using the methods of molecular biology, immunocytochemistry, fluorescence microscopy and inhibitory analysis, the cytoprotective effect of cerium oxide nanoparticles obtained by laser ablation on cultured astrocytes of the cerebral cortex under oxygen-glucose deprivation (OGD) and reoxygenation (ischemia-like conditions) are shown. The concentration effects of cerium oxide nanoparticles on ROS production by astrocytes in an acute experiment and the effects of cell pre-incubation with nanocerium on ROS production under OGD conditions were studied. The dose dependence for nanocerium protection of cortical astrocytes from a global increase in calcium ions during oxygen-glucose deprivation and cell death were demonstrated. The concentration range of cerium oxide nanoparticles at which they have a pro-oxidant effect on cells has been identified. The effect of nanocerium concentrations on astrocyte preconditioning, accompanied by increased expression of protective proteins and limited ROS production induced by oxygen-glucose deprivation, has been investigated. In particular, a correlation was found between an increase in the concentration of cytosolic calcium under the action of nanocerium and the suppression of cell death. As a result, the positive and negative effects of nanocerium under oxygen-glucose deprivation and reoxygenation in astrocytes were revealed at the molecular level. Nanocerium was found to act as a "double-edged sword" and to have a strictly defined concentration therapeutic "window".
大多数旨在研究纳米铈细胞保护特性的工作通常聚焦于细胞内氧化还原状态的调节机制，而纳米铈对钙稳态、促凋亡蛋白和保护蛋白表达的复杂影响通常被忽视。存在一个问题，即氧化铈纳米颗粒的效应强烈依赖于其尺寸、制备方法和来源，这显著限制了它们在医学中的应用。在本研究中，使用分子生物学、免疫细胞化学、荧光显微镜和抑制分析方法，展示了通过激光烧蚀获得的氧化铈纳米颗粒对氧糖剥夺（OGD）和复氧（缺血样条件）下培养的大脑皮质星形胶质细胞的细胞保护作用。研究了氧化铈纳米颗粒在急性实验中对星形胶质细胞产生活性氧（ROS）的浓度效应，以及纳米铈预孵育细胞对OGD条件下ROS产生的影响。证明了纳米铈在氧糖剥夺期间保护皮质星形胶质细胞免受钙离子整体增加和细胞死亡的剂量依赖性。确定了氧化铈纳米颗粒对细胞具有促氧化作用的浓度范围。研究了纳米铈浓度对星形胶质细胞预处理的影响，其伴随着保护蛋白表达增加和氧糖剥夺诱导的ROS产生受限。特别是，发现纳米铈作用下细胞溶质钙浓度的增加与细胞死亡的抑制之间存在相关性。结果，在分子水平上揭示了纳米铈在氧糖剥夺和复氧条件下对星形胶质细胞的正负效应。发现纳米铈起到了“双刃剑”的作用，并具有严格定义的浓度治疗“窗口”。
