Bakshi Mayur V, Barjaktarovic Zarko, Azimzadeh Omid, Kempf Stefan J, Merl Juliane, Hauck Stefanie M, Eriksson Per, Buratovic Sonja, Atkinson Michael J, Tapio Soile
Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg, Germany.
Radiat Environ Biophys. 2013 Nov;52(4):451-61. doi: 10.1007/s00411-013-0483-8. Epub 2013 Jul 24.
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 (60)Co 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.
流行病学研究表明，儿童和年轻人尤其易患辐射诱发的心血管疾病（CVD）。年轻时暴露后心血管疾病风险升高背后的生物学机制尚不清楚。本研究旨在通过研究低剂量和中等剂量辐射暴露后小鼠的心脏蛋白质组，阐明电离辐射的长期影响。NMRI小鼠在出生后第10天接受单次全身（60）Coγ射线照射，并在7个月后处死。使用同位素编码蛋白质标签和串联质谱法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 Gy剂量后鉴定出32、31、66和34种显著失调的蛋白质。这四个剂量共有9种失调蛋白质。生物信息学分析表明，大多数失调蛋白质属于有限的一组生物学类别，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被预测为几种失调蛋白质的共同上游调节因子。本研究表明，对初始辐射损伤的适应性和适应不良反应在成年后仍持续存在。它将有助于理解辐射诱发损伤和新生儿心脏发育改变的长期后果。
