The role of ferroptosis mediated by NRF2/ERK-regulated ferritinophagy in CdTe QDs-induced inflammation in macrophage

J Hazard Mater. 2022 Aug 15;436:129043. doi: 10.1016/j.jhazmat.2022.129043. Epub 2022 May 4.

Abstract

Cadmium telluride quantum dots (CdTe QDs) exist in the environment due to the abandonment of products. There is a potential risk to organisms and toxic mechanism is worth exploring. In this study, 12.5 μmol/Kg body weight CdTe QDs triggered systemic and local inflammatory response in mice and activated macrophages, then the mechanism of activating macrophages to overexpress IL-1β and IL-6 was explored. RAW264.7 macrophages were used, and after macrophages exposing to 1 μM CdTe QDs for 24 h, oxidative stress occurred. Further investigation found that CdTe QDs triggered ferroptosis in RAW264.7 cells. And deferoxamine mesylate alleviated the excessive lipid hydroperoxide caused by QDs. Mechanistically, CdTe QDs-provoked decrease of nuclear factor erythroid 2-related factor 2 (NRF2) elicited phosphorylation of extracellular regulated protein kinases1/2 (ERK1/2) and then activated ferritinophagy, which made ferritin heavy chain 1 (FTH1) degraded in lysosome and proteasome to release free iron ions to initiate ferroptosis in macrophages. This paper updates the mechanism of macrophage activation by CdTe QDs with regard to ferritinophagy, and more importantly, identifies the key role of NRF2 and ERK1/2. Our research extends the role of ferroptosis in inflammatory responses triggered by nanoparticles (NPs) in macrophages and provides insightful reference for toxicity assessment of NPs.

Keywords: CdTe QDs; Ferritinophagy; Ferroptosis; Inflammation; Toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadmium Compounds* / toxicity
  • Ferroptosis*
  • Inflammation / chemically induced
  • Macrophages / metabolism
  • Mice
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Quantum Dots* / toxicity
  • Tellurium / toxicity

Substances

  • Cadmium Compounds
  • NF-E2-Related Factor 2
  • Tellurium
  • cadmium telluride