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

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 β_5i were assessed. Results: Nano-curcumin (5-100 μ<smlcap>M</smlcap>) did not show significant cytotoxicity or anti-oxidative effects against H₂O₂-induced oxidative stress, whereas curcumin (≥10 μ<smlcap>M</smlcap>) 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 β_5i/β₁ and reduced activity of β₅/β_1i. 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.

Whole-Exome sequencing analysis identified TMSB10/TRABD2A locus to be associated with carfilzomib-related cardiotoxicity among patients with multiple myeloma

“…This study concluded that patients who received CFZ and with low potential for proteasome activity recovery may suffer from both acute and long-term endothelial dysfunction (48). Endothelial cell homeostasis depends on the ubiquitinproteasome system, which induces oxidative stress in the cells and regulates the expression of endothelial nitric oxide synthase (49). The proteasome inhibitor CFZ causes the plasma of cancer cells, cardiomyocytes, and endothelial cells to accumulate with unfolded, dysfunctional proteins, which may lead to impaired vasodilation, excessive oxidative stress, inflammation, cell apoptosis, and autophagy (50,51).…”

SPI1-mediated macrophage polarization aggravates age-related macular degeneration

“…It has significant effects on cell migration, tumor development, and angiogenesis. Epoxomicin may lead to an imbalance between MMP-2 and TIMP-1 in ARPE-19 cells, resulting in the occurrence of retinal fibrosis (37). Since in most cases, transcription factors (TFs) are always the key regulators of gene expression and cellular functions, and their dysregulation has been implicated in various pathological conditions including neovascular diseases (38,39), we focused on the only TF among the top 10 pivotal DEGs, SPI1, for further study.…”