Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor Cells.

Particle Radiation-Induced Nontargeted Effects in Bone-Marrow-Derived Endothelial Progenitor Cells.
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DOI:
10.1155/2015/496512
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发表时间:
2015
影响因子:
4.3
通讯作者:
Goukassian DA
Goukassian DA
中科院分区:
医学3区
文献类型:
--
作者:
Sasi SP;Park D;Muralidharan S;Wage J;Kiladjian A;Onufrak J;Enderling H;Yan X;Goukassian DA

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骨髓来源的内皮祖细胞(EPCs)对于内皮细胞的维持和修复至关重要。在未来的太空探索任务中,宇航员将暴露于由低通量质子(1H)和高电荷和能量(HZE)核(例如,铁-56 Fe)。空间型IR对BM-EPCs的影响是有限的。在体外培养基转移实验中,我们研究了1H-和56 Fe-IR条件培养基(CM)诱导的非靶向效应,其显示在未照射的EPCs中p-H2 AX灶的数量在2和24 h之间显著增加。在24 h时,在两种类型的IR-CM中观察到各种细胞因子和趋化因子的水平增加2-15倍。来自单次、低剂量、全身1H-和56 Fe-IR小鼠的BM-EPCs的离体分析表明细胞凋亡周期性(早期5-24小时和延迟28天)增加。BM-EPC凋亡的早期增加可能是直接IR暴露的影响,而凋亡的晚期增加可能是IR未直接穿过的细胞中的非靶向效应(NTE)的结果。确定负责IR诱导的NTE的特定细胞因子的作用并抑制此类NTE可以防止BM环境中干细胞和祖细胞的长期和周期性损失。
Bone-marrow- (BM-) derived endothelial progenitor cells (EPCs) are critical for endothelial cell maintenance and repair. During future space exploration missions astronauts will be exposed to space irradiation (IR) composed of a spectrum of low-fluence protons (1H) and high charge and energy (HZE) nuclei (e.g., iron-56Fe) for extended time. How the space-type IR affects BM-EPCs is limited. In media transfer experiments in vitro we studied nontargeted effects induced by 1H- and 56Fe-IR conditioned medium (CM), which showed significant increase in the number of p-H2AX foci in nonirradiated EPCs between 2 and 24 h. A 2–15-fold increase in the levels of various cytokines and chemokines was observed in both types of IR-CM at 24 h. Ex vivo analysis of BM-EPCs from single, low-dose, full-body 1H- and 56Fe-IR mice demonstrated a cyclical (early 5–24 h and delayed 28 days) increase in apoptosis. This early increase in BM-EPC apoptosis may be the effect of direct IR exposure, whereas late increase in apoptosis could be a result of nontargeted effects (NTE) in the cells that were not traversed by IR directly. Identifying the role of specific cytokines responsible for IR-induced NTE and inhibiting such NTE may prevent long-term and cyclical loss of stem and progenitors cells in the BM milieu.
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