Metal Oxide Nanoparticle-Induced Changes in 20S Proteasome Activity

C.A. Falaschetti, T. Paunesku, S.S. Chou, M.H. Song, J-T Jang, V.P. Dravid, J. Cheon, G.E. Woloschak
Northwestern University, Feinberg School of Medicine, US

Keywords: titanium dioxide nanoparticles, iron oxide nanoparticles, 20S proteasome

Summary:

The multicatalytic ubiquitin-proteasome system (UPS) is responsible for protein degradation as well as the regulation of a vast number of crucial cellular processes. The UPS is a drug target for many diseases, including cancer, where increased proteasomal activity results in enhanced tumorigenesis. Metal oxide nanoparticles are increasingly used as contrast agents for medical imaging and as potential therapeutic delivery vehicles. Cytotoxicity studies have revealed that metal oxide nanoparticle treatment results in the disruption of processes regulated by the UPS such as cell-cycle progression, protein expression, and apoptosis. However, metal oxide nanoparticles have not previously been tested as modulators of proteasomal activity. Here, several iron oxide (Fe3O4) and titanium dioxide (TiO2) nanoparticles varying in size, shape, and surface coating were incubated with purified 20S proteasome protein, and many were found to enhance proteasome activity in a physiochemical-, concentration-, and time-dependent manner. Overall, this study lends valuable information pertaining to a potential mechanism of metal oxide nanoparticle-induced cytotoxicity. Future work will address the feasibility of using metal oxide nanoparticles in relevant therapeutic applications such as the treatment of various neurodegenerative diseases and viral infections that are associated with decreased proteasomal activity.