Negatively charged metal oxide nanoparticles interact with the 20S proteasome and differentially modulate its biologic functional effects

Christine A. Falaschetti, Tatjana Paunesku, Jasmina Kurepa, Dhaval Nanavati, Stanley S. Chou, Mrinmoy De, Minha Song, Jung Tak Jang, Aiguo Wu, Vinayak P. Dravid, Jinwoo Cheon, Jan Smalle, Gayle E. Woloschak

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14 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7759-7772
Number of pages14
JournalACS Nano
Volume7
Issue number9
DOIs
Publication statusPublished - 2013 Sep 24

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All Science Journal Classification (ASJC) codes

  • Materials Science(all)
  • Engineering(all)
  • Physics and Astronomy(all)

Cite this

Falaschetti, C. A., Paunesku, T., Kurepa, J., Nanavati, D., Chou, S. S., De, M., Song, M., Jang, J. T., Wu, A., Dravid, V. P., Cheon, J., Smalle, J., & Woloschak, G. E. (2013). Negatively charged metal oxide nanoparticles interact with the 20S proteasome and differentially modulate its biologic functional effects. ACS Nano, 7(9), 7759-7772. https://doi.org/10.1021/nn402416h