Long-term effects of acute low-dose ionizing radiation on the neonatal mouse heart: a proteomic study
Long-term effects of acute low-dose ionizing radiation on the neonatal mouse heart: a proteomic study
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DOI：
10.1007/s00411-013-0483-8
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发表时间：
2013-11-01
影响因子：
1.7
通讯作者：
Tapio, Soile
中科院分区：
文献类型：
--
作者：
Bakshi, Mayur V.;Barjaktarovic, Zarko;Tapio, Soile
流行病学研究证实，儿童和青年人特别容易受到辐射诱发的心血管疾病的影响。年轻时暴露后CVD风险升高的生物学机制仍然未知。本研究的目的是阐明电离辐射的长期影响，通过研究小鼠心脏蛋白质组暴露于低和中等剂量的辐射后。NMRI小鼠在出生后第10天接受单次全身Co-60 γ射线照射，7个月后处死。使用同位素编码的蛋白质标记和串联质谱定量心脏蛋白质表达的变化。我们分别在0.02、0.1、0.5和1.0戈伊剂量后鉴定了32、31、66和34种显著失调的蛋白质。四种剂量共有9种失调蛋白。生物信息学分析表明，大多数去调控的蛋白质属于有限的生物学类别，包括代谢过程，炎症反应和细胞骨架结构。转录因子过氧化物酶体增殖物激活受体α被预测为几种去调节蛋白质的共同上游调节因子。这项研究表明，适应和适应不良的反应，最初的辐射损伤持续到成年。它将有助于了解辐射引起的损伤和新生儿心脏发育改变的长期后果。
Epidemiological studies establish that children and young adults are especially susceptible to radiation-induced cardiovascular disease (CVD). The biological mechanisms behind the elevated CVD risk following exposure at young age remain unknown. The present study aims to elucidate the long-term effects of ionizing radiation by studying the murine cardiac proteome after exposure to low and moderate radiation doses. NMRI mice received single doses of total body Co-60 gamma-irradiation on postnatal day 10 and were sacrificed 7 months later. Changes in cardiac protein expression were quantified using isotope-coded protein label and tandem mass spectrometry. We identified 32, 31, 66, and 34 significantly deregulated proteins after doses of 0.02, 0.1, 0.5, and 1.0 Gy, respectively. The four doses shared 9 deregulated proteins. Bioinformatics analysis showed that most of the deregulated proteins belonged to a limited set of biological categories, including metabolic processes, inflammatory response, and cytoskeletal structure. The transcription factor peroxisome proliferator-activated receptor alpha was predicted as a common upstream regulator of several deregulated proteins. This study indicates that both adaptive and maladaptive responses to the initial radiation damage persist well into adulthood. It will contribute to the understanding of the long-term consequences of radiation-induced injury and developmental alterations in the neonatal heart.