Modulation of the proteasome pathway by nano-curcumin and curcumin in retinal pigment epithelial cellsCarvalho, J. Emanuel Ramos de (Avtor) Verwoert, Milan T. (Avtor) Vogels, Ilse M.C. (Avtor) Schipper-Krom, Sabine (Avtor) Noorden, Cornelis J. F. van (Avtor) Reits, Eric A. (Avtor) Klaassen, Ingeborg (Avtor) Schlingemann, Reinier O. (Avtor) curcuminnano-curcuminproteasomeretinal pigment epitheliumIntroduction: Curcumin has multiple biological effects including the modulation of protein homeostasis by the ubiquitin-proteasome system. The purpose of this study was to assess the in vitro cytotoxic and oxidative effects of nano-curcumin and standard curcumin and characterize their effects on proteasome regulation in retinal pigment epithelial (RPE) cells. Methods: Viability, cell cycle progression, and reactive oxygen species (ROS) production were determined after treatment with nano-curcumin or curcumin. Subsequently, the effects of nano-curcumin and curcumin on proteasome activity and the gene and protein expression of proteasome subunits PA28α, α7, β5, and β5i were assessed. Results: Nano-curcumin (5-100 μM) did not show significant cytotoxicity or anti-oxidative effects against H2O2-induced oxidative stress, whereas curcumin (≥10 μM) was cytotoxic and a potent inducer of ROS production. Both nano-curcumin and curcumin induced changes in proteasome-mediated proteolytic activity characterized by increased activity of the proteasome subunits β2 and β5i/β1 and reduced activity of β5/β1i. Likewise, nano-curcumin and curcumin affected mRNA and protein levels of household and immunoproteasome subunits. Conclusions: Nano-curcumin is less toxic to RPE cells and less prone to induce ROS production than curcumin. Both nano-curcumin and curcumin increase proteasome-mediated proteolytic activity. These results suggest that nano-curcumin may be regarded as a proteasome-modulating agent of limited cytotoxicity for RPE cells. 20182025-02-26 11:49:18Neznano21552UDK: 617.7ISSN pri članku: 0030-3747DOI: 10.1159/000481261COBISS_ID: 4640591sl