Modulation of the Proteasome Pathway by Nano-Curcumin and Curcumin in Retinal Pigment Epithelial Cells

Ophthalmic Res. 2018;59(2):98-109. doi: 10.1159/000481261. Epub 2017 Oct 27.

Abstract

Introduction: 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.

Keywords: Curcumin; Nano-curcumin; Proteasome; Retinal pigment epithelium.

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cell Cycle / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Curcumin / pharmacology*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Humans
  • Oxidative Stress / drug effects
  • Proteasome Endopeptidase Complex / metabolism*
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Retinal Pigment Epithelium / drug effects*
  • Retinal Pigment Epithelium / metabolism
  • Retinal Pigments / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • RNA, Messenger
  • Reactive Oxygen Species
  • Retinal Pigments
  • Proteasome Endopeptidase Complex
  • Curcumin