Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process.

Low dose radiation induced senescence of human mesenchymal stromal cells and impaired the autophagy process.
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低剂量辐射诱导人间充质基质细胞的衰老并损害自噬过程。

DOI:
10.18632/oncotarget.2692
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发表时间:
2015-04-10
期刊:
影响因子:
--
通讯作者:
Galderisi U
Galderisi U
中科院分区:
其他
文献类型:
--
作者:
Alessio N;Del Gaudio S;Capasso S;Di Bernardo G;Cappabianca S;Cipollaro M;Peluso G;Galderisi U

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低剂量辐射可能会对细胞功能产生深远影响。个人可能出于医疗目的或意外地暴露于低剂量辐射,例如暴露于放射性恐怖主义的人或生活在非法放射性废物倾倒场附近的人。我们研究了低剂量辐射对人骨髓间充质基质细胞(MSC)的影响,MSC含有一种干细胞亚群,能够在骨、软骨和脂肪中分化,支持造血,并有助于人体的内环境稳定。低剂量辐射除了减少细胞周期外,主要的结果是引发衰老,而对细胞凋亡的贡献很小。我们还发现,低辐射对自噬通量有影响。我们假设,自噬阻止了辐射的恶化过程,它的下降导致了衰老。照射后1小时和6小时ATM染色增加,48小时恢复到基础水平,以及持续的伽马-H_2AX染色,表明MSC正确地激活了DNA修复信号,尽管一些损伤仍未修复,主要是在非周期细胞中。提示照射后MSC的DNA修复能力受损可能主要与非同源末端连接(NHEJ)系统活性降低有关,而与同源重组(HR)无关。
Low doses of radiation may have profound effects on cellular function. Individuals may be exposed to low doses of radiation either intentionally for medical purposes or accidentally, such as those exposed to radiological terrorism or those who live near illegal radioactive waste dumpsites. We studied the effects of low dose radiation on human bone marrow mesenchymal stromal cells (MSC), which contain a subpopulation of stem cells able to differentiate in bone, cartilage, and fat; support hematopoiesis; and contribute to body's homeostasis. The main outcome of low radiation exposure, besides reduction of cell cycling, is the triggering of senescence, while the contribution to apoptosis is minimal. We also showed that low radiation affected the autophagic flux. We hypothesize that the autophagy prevented radiation deteriorative processes, and its decline contributed to senescence. An increase in ATM staining one and six hours post-irradiation and return to basal level at 48 hours, along with persistent gamma-H2AX staining, indicated that MSC properly activated the DNA repair signaling, though some damages remained unrepaired, mainly in non-cycling cells. This suggested that the impaired DNA repair capacity of irradiated MSC seemed mainly related to the reduced activity of a non-homologous end-joining (NHEJ) system rather than HR (homologous recombination).
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