A proteomic approach to identification of plutonium-binding proteins in mammalian cells.

A proteomic approach to identification of plutonium-binding proteins in mammalian cells.
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DOI:
10.1016/j.jprot.2011.11.023
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发表时间:
2012-02-16
影响因子:
3.3
通讯作者:
Jensen MP
Jensen MP
中科院分区:
生物学2区
文献类型:
--
作者:
Aryal BP;Paunesku T;Woloschak GE;He C;Jensen MP

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钚可以通过不同的途径进入人体,并在那里停留数十年;然而,其特定的生化相互作用尚不清楚。我们首次使用金属蛋白质组学方法研究了大鼠PC12细胞的钚结合蛋白。采用固定化金属离子层析、双向凝胶电泳法和质谱法相结合的方法对潜在的钚结合蛋白进行分析。我们的结果表明,来自PC12细胞的几种蛋白质对Pu4+-NTA(与氮三乙酸结合的钚)具有亲和力。鉴定了来自2D凝胶中七个不同点的蛋白质。与先前已知的钚结合蛋白转铁蛋白和铁蛋白结合铁离子不同,我们实验中发现的大多数蛋白质都与钙、镁或二价过渡金属离子结合。已鉴定的钚相互作用蛋白还在下调细胞凋亡和其他促增殖过程中发挥作用。基于这组蛋白质的MetaCore分析产生了一个与肿瘤疾病的发展具有统计学意义的关联的途径。
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 were employed to analyze potential plutonium-binding proteins. Our results show that several proteins from PC12 cells show affinity towards Pu4+-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.
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