Feinberg School of Medicine, Department of Radiation Oncology, Northwestern University , Chicago, Illinois 60611, United States.
ACS Nano. 2013 Sep 24;7(9):7759-72. doi: 10.1021/nn402416h. Epub 2013 Aug 20.
The multicatalytic ubiquitin-proteasome system (UPS) carries out proteolysis in a highly orchestrated way and regulates a large number of cellular processes. Deregulation of the UPS in many disorders has been documented. In some cases, such as carcinogenesis, elevated proteasome activity has been implicated in disease development, while the etiology of other diseases, such as neurodegeneration, includes decreased UPS activity. Therefore, agents that alter proteasome activity could suppress as well as enhance a multitude of diseases. Metal oxide nanoparticles, often developed as diagnostic tools, have not previously been tested as modulators of proteasome activity. Here, several types of metal oxide nanoparticles were found to adsorb to the proteasome and show variable preferential binding for particular proteasome subunits with several peptide binding "hotspots" possible. These interactions depend on the size, charge, and concentration of the nanoparticles and affect proteasome activity in a time-dependent manner. Should metal oxide nanoparticles increase proteasome activity in cells, as they do in vitro, unintended effects related to changes in proteasome function can be expected.
多催化泛素蛋白酶体系统 (UPS) 以高度协调的方式进行蛋白水解，并调节大量细胞过程。UPS 在许多疾病中的失调已被记录在案。在某些情况下，如癌症发生，较高的蛋白酶体活性与疾病发展有关，而其他疾病的病因，如神经退行性疾病，则包括 UPS 活性降低。因此，改变蛋白酶体活性的试剂既可以抑制也可以增强多种疾病。金属氧化物纳米粒子通常作为诊断工具开发，以前从未被测试过作为蛋白酶体活性调节剂。在这里，几种类型的金属氧化物纳米粒子被发现吸附到蛋白酶体上，并显示出对特定蛋白酶体亚基的可变优先结合，可能存在几个肽结合“热点”。这些相互作用取决于纳米粒子的大小、电荷和浓度，并以时间依赖性的方式影响蛋白酶体活性。如果金属氧化物纳米粒子像在体外那样增加细胞内的蛋白酶体活性，那么可以预期与蛋白酶体功能变化相关的意外影响。
