Chemical Science and Engineering Division, Argonne National Lab, Argonne, IL, USA.
J Proteomics. 2012 Feb 16;75(5):1505-14. doi: 10.1016/j.jprot.2011.11.023. Epub 2011 Dec 3.
Plutonium can enter the body through different routes and remains there for decades; however its specific biochemical interactions are poorly defined. We, for the first time, have studied plutonium-binding proteins using a metalloproteomic approach with rat PC12 cells. A combination of immobilized metal ion chromatography, 2D gel electrophoresis, and mass spectrometry was employed to analyze potential plutonium-binding proteins. Our results show that several proteins from PC12 cells show affinity towards Pu(4+)-NTA (plutonium bound to nitrilotriacetic acid). Proteins from seven different spots in the 2D gel were identified. In contrast to the previously known plutonium-binding proteins transferrin and ferritin, which bind ferric ions, most identified proteins in our experiment are known to bind calcium, magnesium, or divalent transition metal ions. The identified plutonium interacting proteins also have functional roles in downregulation of apoptosis and other pro-proliferative processes. MetaCore™ analysis based on this group of proteins produced a pathway with a statistically significant association with development of neoplastic diseases.
钚可以通过不同的途径进入人体，并在体内停留数十年；然而，其具体的生化相互作用尚未得到明确界定。我们首次使用金属蛋白质组学方法在大鼠 PC12 细胞中研究了钚结合蛋白。我们采用固定化金属离子亲和色谱、二维凝胶电泳和质谱联用的方法来分析潜在的钚结合蛋白。结果表明，来自 PC12 细胞的几种蛋白对 Pu(4+)-NTA（与氮三乙酸结合的钚）具有亲和力。从二维凝胶中的七个不同斑点中鉴定出蛋白质。与先前已知的钚结合蛋白转铁蛋白和铁蛋白（结合三价铁离子）不同，我们实验中大多数鉴定出的蛋白已知结合钙、镁或二价过渡金属离子。鉴定出的钚相互作用蛋白在下调细胞凋亡和其他促增殖过程中也具有功能作用。基于该组蛋白的 MetaCore™分析产生了一条与肿瘤性疾病发展具有统计学显著关联的通路。
