Pluder Franka, Barjaktarovic Zarko, Azimzadeh Omid, Mörtl Simone, Krämer Anne, Steininger Sylvia, Sarioglu Hakan, Leszczynski Dariusz, Nylund Reetta, Hakanen Arvi, Sriharshan Arundhathi, Atkinson Michael J, Tapio Soile
Institute of Radiation Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Ingolstaedter Landstrasse 1, 85764, Neuherberg, Germany.
Radiat Environ Biophys. 2011 Mar;50(1):155-66. doi: 10.1007/s00411-010-0342-9. Epub 2010 Nov 23.
High doses of ionising radiation damage the heart by an as yet unknown mechanism. A concern for radiological protection is the recent epidemiological data indicating that doses as low as 100-500 mGy may induce cardiac damage. The aim of this study was to identify potential molecular targets and/or mechanisms involved in the pathogenesis of low-dose radiation-induced cardiovascular disease. The vascular endothelium plays a pivotal role in the regulation of cardiac function and is therefore a potential target tissue. We report here that low-dose radiation induced rapid and time-dependent changes in the cytoplasmic proteome of the human endothelial cell line EA.hy926. The proteomes were investigated at 4 and 24 h after irradiation at two different dose rates (Co-60 gamma ray total dose 200 mGy; 20 mGy/min and 190 mGy/min) using 2D-DIGE technology. Differentially expressed proteins were identified, after in-gel trypsin digestion, by MALDI-TOF/TOF tandem mass spectrometry, and peptide mass fingerprint analyses. We identified 15 significantly differentially expressed proteins, of which 10 were up-regulated and 5 down-regulated, with more than ±1.5-fold difference compared with unexposed cells. Pathways influenced by the low-dose exposures included the Ran and RhoA pathways, fatty acid metabolism and stress response.
高剂量电离辐射会通过一种尚不清楚的机制损害心脏。放射防护方面的一个担忧是最近的流行病学数据表明,低至100 - 500毫戈瑞的剂量可能会诱发心脏损伤。本研究的目的是确定低剂量辐射诱发心血管疾病发病机制中涉及的潜在分子靶点和/或机制。血管内皮在心脏功能调节中起关键作用,因此是一个潜在的靶组织。我们在此报告,低剂量辐射会在人内皮细胞系EA.hy926的细胞质蛋白质组中诱导快速且随时间变化的改变。使用二维差异凝胶电泳(2D - DIGE)技术,在两种不同剂量率(钴 - 60γ射线总剂量200毫戈瑞;20毫戈瑞/分钟和190毫戈瑞/分钟)照射后的4小时和24小时对蛋白质组进行了研究。经凝胶内胰蛋白酶消化后,通过基质辅助激光解吸电离飞行时间串联质谱(MALDI - TOF/TOF)和肽质量指纹分析鉴定差异表达的蛋白质。我们鉴定出15种显著差异表达的蛋白质,其中10种上调,5种下调,与未暴露细胞相比差异超过±1.5倍。受低剂量照射影响的信号通路包括Ran和RhoA信号通路、脂肪酸代谢和应激反应。