Space particle radiations may cause significant damage to proteins and oxidative stress in the cells within the central nervous system and pose a potential health hazard to humans in long-term manned space explorations. Dysregulation of the ubiquitin-proteasome system as evidenced by abnormal accumulation of polyubiquitin (pUb) chain linkages has been implicated in several age-related neurodegenerative disorders by mechanisms that may involve the inter-neuronal spread of toxic misfolded proteins, the induction of chronic neuroinflammation, or the inappropriate inhibition or activation of key enzymes, which could lead to dysfunction in, for example, proteolysis, or the accumulation of post-translationally-modified substrates.In this study, we employed a quantitative proteomics method to evaluate the impact of particle-radiation induced alterations in three major pUb-linked chains at lysine residues Lys-48 (K-48), Lys-63 (K-63), and Lys-11 (K-11), and probed for global proteomic changes in mouse and human neural cells that were irradiated with low doses of 250 MeV proton, 260 MeV/u silicon or 1 GeV/u iron ions. We found significant accumulation in K-48 linkage after 1 Gy protons and K-63 linkage after 0.5 Gy iron ions in human neural cells. Cells derived from different regions of the mouse brain (cortex, striatum and mesencephalon) showed differential sensitivity to particle radiation exposure. Although none of the linkages were altered after proton exposure, both K-48 and K-63 linkages in mouse striatal neuronal cells were elevated after 0.5 Gy of silicon or iron ions. Changes were also seen in proteins commonly used as markers of neural progenitor and stem cells, in DNA binding/damage repair and cellular redox pathways. In contrast, no significant changes were observed at the same time point after proton irradiation. These results suggest that the quality of the particle radiation plays a key role in the level, linkage and cell type specificity of protein homeostasis in key populations of neuronal cells.

空间粒子辐射可能会对中枢神经系统内的细胞中的蛋白质和氧化应激造成重大损害，并在长期有人驾驶的太空探索中对人体构成潜在的健康危害。多聚泛素（pUb）链连接异常积累所证明的泛素-蛋白酶体系统失调，可能与多种年龄相关的神经退行性疾病有关，其机制可能涉及神经元间毒性错折叠蛋白的扩散，诱导慢性神经炎症，或关键酶的不适当抑制或激活，可能导致例如蛋白水解或翻译后修饰底物积聚的功能障碍。我们采用定量蛋白质组学方法来评估粒子辐射诱导的赖氨酸残基Lys-48（K-48），Lys-63（K-63）和Lys-11（K -11），并探测了用低剂量250 MeV质子，260 MeV / u硅或1 GeV / u铁离子辐照的小鼠和人类神经细胞的整体蛋白质组学变化。我们发现人类神经细胞中1 Gy质子后在K-48键和K-63键中显着积累在0.5 Gy铁离子之后。来自小鼠大脑不同区域（皮层，纹状体和中脑）的细胞对粒子辐射暴露具有不同的敏感性。尽管质子暴露后这些键都没有改变，但是在0.5 Gy的硅或铁离子作用下，小鼠纹状体神经元细胞中的K-48和K-63键都升高了。在通常用作神经祖细胞和干细胞标志物的蛋白质，DNA结合/损伤修复和细胞氧化还原途径中也观察到了变化。相反，在质子辐照后的同一时间点没有观察到明显的变化。这些结果表明，粒子辐射的质量在神经细胞关键群体中蛋白质稳态的水平，连锁和细胞类型特异性中起着关键作用。