Gold nanourchins induce cellular stress, impair proteostasis and damage RNA

Nanomedicine. 2019 Nov:22:102083. doi: 10.1016/j.nano.2019.102083. Epub 2019 Aug 9.

Abstract

Gold nanoparticles have excellent potential for theranostic applications, but their impact on living cells is only partially understood. Many gold nanoparticles enter cells through endosomes/lysosomes which are linked to different cell organelles and compartments. Our study focuses on the unfolded protein response (UPR) in the endoplasmic reticulum (ER), cytoplasmic RNA-granules and proteostasis, because they are established indicators of cell stress and key regulators of cellular homeostasis. Using HeLa and renal proximal tubule cells as model systems, we show that gold nanourchins reduce cell proliferation, cause ER stress and impair proteostasis. Specifically, gold nanourchins activate the PERK-branch of the UPR, promote RNA oxidation, enhance P-body formation, and accumulate the oxidative stress marker Nrf2 and NFκB in nuclei. Taken together, our study demonstrates that gold nanourchins compromise ER, redox, protein, and RNA homeostasis. These insights provide new information on the cellular responses and molecular changes that gold nanourchins elicit in mammalian cells.

Keywords: Endoplasmic reticulum stress; Gold nanourchins; Oxidative stress; Proteostasis; Unfolded protein response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Apoptosis / drug effects
  • Biomarkers / metabolism
  • Cell Proliferation / drug effects
  • Cytoplasm / metabolism
  • Endoplasmic Reticulum Stress / drug effects
  • Gold / toxicity*
  • HeLa Cells
  • Humans
  • LLC-PK1 Cells
  • Metal Nanoparticles / toxicity*
  • Models, Biological
  • NF-E2-Related Factor 2 / metabolism
  • NF-kappa B / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Particle Size
  • Proteostasis / drug effects*
  • RNA / genetics*
  • Stress, Physiological / drug effects*
  • Swine
  • Unfolded Protein Response / drug effects

Substances

  • Antioxidants
  • Biomarkers
  • NF-E2-Related Factor 2
  • NF-kappa B
  • NFE2L2 protein, human
  • RNA
  • Gold