The MRI marker gene MagA attenuates the oxidative damage induced by iron overload in transgenic mice

Nanotoxicology. 2016;10(5):531-41. doi: 10.3109/17435390.2015.1090029. Epub 2015 Oct 21.

Abstract

We aimed to create transgenic (Tg) mice engineered for magnetic resonance imaging (MRI). To ascertain if MagA expression contributes to oxidative stress and iron metabolism, we report the generation of Tg mice in which ubiquitous expression of MagA can be detected by MRI in vivo. Expression of MagA in diverse tissues of Tg mice was assessed, and iron accumulation and deposition of nanoparticles in tissues were analyzed. Levels of antioxidant enzymes, lipid peroxidation and cytokine production were determined, and iron metabolism-related proteins were also detected. MagA Tg showed no apparent pathologic symptoms and no histologic changes compared with wild-type (WT) mice. Overexpression of MagA resulted in specific alterations of the transverse relaxation rate (R2) of water. Transgene-dependent changes in R2 were detectable by MRI in iron-overloaded mice. We also evaluated antioxidant abilities between WT and Tg groups or two iron-overloaded groups. Together with the data of cytokines and iron metabolism-related proteins, we inferred that MagA could regulate nanoparticle production and thus attenuate the oxidative damage induced by iron overload. The novel MagA Tg mouse, which expresses an MRI reporter in many tissues, would be a valuable model of MagA molecular imaging in which to study diseases related to iron metabolism.

Keywords: Iron overload; MagA; magnetic resonance imaging; oxidative stress; transgenic mouse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / genetics*
  • Biomarkers / metabolism
  • Blotting, Western
  • Cation Transport Proteins / genetics*
  • Female
  • Genes, Reporter
  • Iron / chemistry
  • Iron / metabolism
  • Iron / toxicity*
  • Iron Overload / diagnosis*
  • Iron Overload / genetics
  • Iron Overload / metabolism
  • Liver / enzymology
  • Liver / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / toxicity*
  • Mice
  • Mice, Transgenic*
  • Microscopy, Electron, Transmission
  • Oxidative Stress* / genetics
  • Spectrophotometry, Atomic
  • Tissue Distribution

Substances

  • Bacterial Proteins
  • Biomarkers
  • Cation Transport Proteins
  • MagA protein, Magnetospirillum
  • Iron