DOI: 10.1016/j.lssr.2020.02.003
论文题名: Particle radiation-induced dysregulation of protein homeostasis in primary human and mouse neuronal cells
作者: Shaler T. ; Lin H. ; Bakke J. ; Chen S. ; Grover A. ; Chang P.
刊名: Life Sciences in Space Research
ISSN: 22145524
出版年: 2020
卷: 25 语种: 英语
英文关键词: Neuronal cells
; Particle radiation
; Protein ubiquitination
Scopus关键词: DNA binding protein
; iron
; lysine
; polyubiquitin
; proteasome
; protein
; proton
; silicon
; animal cell
; animal cell culture
; Article
; brain cortex
; brain nerve cell
; cell population
; controlled study
; corpus striatum
; DNA binding
; DNA damage
; DNA repair
; embryo
; human
; human cell
; human cell culture
; in vitro study
; mesencephalon
; mouse
; neural stem cell
; nonhuman
; oxidation reduction state
; oxidative stress
; particle radiation
; priority journal
; protein cross linking
; protein degradation
; protein expression
; protein homeostasis
; protein processing
; proteomics
; proton radiation
; quantitative analysis
; radiation dose
; radiosensitivity
英文摘要: 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. © 2020 The Committee on Space Research (COSPAR) Citation statistics:
资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/158320
Appears in Collections: 气候变化与战略
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作者单位: SRI International, 333 Ravenswood Ave, Menlo Park, CA 94025, United States
Recommended Citation:
Shaler T.,Lin H.,Bakke J.,et al. Particle radiation-induced dysregulation of protein homeostasis in primary human and mouse neuronal cells[J]. Life Sciences in Space Research,2020-01-01,25