Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Radiation Biology, Neuherberg, Germany.
PLoS One. 2013 Aug 1;8(8):e70024. doi: 10.1371/journal.pone.0070024. Print 2013.
The etiology of radiation-induced cardiovascular disease (CVD) after chronic exposure to low doses of ionizing radiation is only marginally understood. We have previously shown that a chronic low-dose rate exposure (4.1 mGy/h) causes human umbilical vein endothelial cells (HUVECs) to prematurely senesce. We now show that a dose rate of 2.4 mGy/h is also able to trigger premature senescence in HUVECs, primarily indicated by a loss of growth potential and the appearance of the senescence-associated markers ß-galactosidase (SA-ß-gal) and p21. In contrast, a lower dose rate of 1.4 mGy/h was not sufficient to inhibit cellular growth or increase SA-ß-gal-staining despite an increased expression of p21. We used reverse phase protein arrays and triplex Isotope Coded Protein Labeling with LC-ESI-MS/MS to study the proteomic changes associated with chronic radiation-induced senescence. Both technologies identified inactivation of the PI3K/Akt/mTOR pathway accompanying premature senescence. In addition, expression of proteins involved in cytoskeletal structure and EIF2 signaling was reduced. Age-related diseases such as CVD have been previously associated with increased endothelial cell senescence. We postulate that a similar endothelial aging may contribute to the increased rate of CVD seen in populations chronically exposed to low-dose-rate radiation.
慢性低剂量电离辐射暴露后放射性心血管疾病（CVD）的病因仅略知一二。我们之前已经表明，慢性低剂量率暴露（4.1 mGy/h）会导致人脐静脉内皮细胞（HUVEC）过早衰老。我们现在表明，剂量率为 2.4 mGy/h 也能够引发 HUVEC 过早衰老，主要表现为生长潜力丧失和衰老相关标志物β-半乳糖苷酶（SA-β-gal）和 p21 的出现。相比之下，尽管 p21 表达增加，但较低的剂量率 1.4 mGy/h 不足以抑制细胞生长或增加 SA-β-gal 染色。我们使用反相蛋白质阵列和三重同位素编码蛋白质标记与 LC-ESI-MS/MS 来研究与慢性辐射诱导衰老相关的蛋白质组变化。这两种技术都确定了 PI3K/Akt/mTOR 通路的失活伴随着过早衰老。此外，参与细胞骨架结构和 EIF2 信号的蛋白质表达减少。以前曾将 CVD 等与年龄相关的疾病与内皮细胞衰老增加联系起来。我们假设，类似的内皮细胞衰老可能导致长期暴露于低剂量率辐射的人群中 CVD 发生率的增加。
