Magnetite nanoparticles induced adaptive mechanisms counteract cell death in human pulmonary fibroblasts

Toxicol In Vitro. 2015 Oct;29(7):1492-502. doi: 10.1016/j.tiv.2015.06.002. Epub 2015 Jun 9.

Abstract

Magnetite nanoparticles (MNP) have attracted great interest for biomedical applications due to their unique chemical and physical properties, but the MNP impact on human health is not fully known. Consequently, our study proposes to highlight the biochemical mechanisms that underline the toxic effects of MNP on a human lung fibroblast cell line (MRC-5). The cytotoxicity generated by MNP in MRC-5 cells was dose and time-dependent. MNP-treated MRC-5 cells accumulated large amount of iron and reactive oxygen species (ROS) and exhibited elevated antioxidant scavenger enzymes. Reduced glutathione (GSH) depletion and enhanced lipid peroxidation (LPO) processes were also observed. The cellular capacity to counteract the oxidative damage was sustained by high levels of heat shock protein 60 (Hsp60), a protein that confers resistance against ROS attack and inhibition of cell death. While significant augmentations in nitric oxide (NO) and prostaglandine E2 (PGE2) levels were detected after 72 h of MNP-exposure only, caspase-1 was activated earlier starting with 24h post-treatment. Taken together, our results suggest that MRC-5 cells have the capacity to develop cell protection mechanisms against MNP. Detailed knowledge of the mechanisms induced by MNP in cell culture could be essential for their prospective use in various in vivo biochemical applications.

Keywords: Caspase-1; Hsp60; MRC-5 cells; Magnetite nanoparticles; Oxidative stress; PGE2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspase 1 / metabolism
  • Catalase / metabolism
  • Cell Death / drug effects
  • Cell Line
  • Chaperonin 60 / genetics
  • Chaperonin 60 / metabolism
  • Dinoprostone / metabolism
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Reductase / metabolism
  • Humans
  • Lung / cytology
  • Magnetite Nanoparticles / toxicity*
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Nitric Oxide / metabolism
  • Reactive Oxygen Species / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • Chaperonin 60
  • HSPD1 protein, human
  • Magnetite Nanoparticles
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Nitric Oxide
  • Catalase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Reductase
  • Caspase 1
  • Dinoprostone