Kidney Toxicity and Response of Selenium Containing Protein-glutathione Peroxidase (Gpx3) to CdTe QDs on Different Levels

Toxicol Sci. 2019 Mar 1;168(1):201-208. doi: 10.1093/toxsci/kfy297.

Abstract

The toxic mechanism of cadmium-quantum dots (Cd-QDs) to organisms is still debating. In this paper, it was found that Cd-QDs could induce adverse effects to kidney by entering into cells in a time and dose manner and disturbing the redox balance in vivo. As a selenium containing protein, glutathione peroxidase3 (Gpx3) plays a crucial role in maintaining the balance of redox system. The decrease in Gpx3 activity might be related to the imbalance of redox system. Similar to the animal results, it was demonstrated that Gpx3 activity is also inhibited by Cd-QDs in vitro. To investigate the underlying mechanism of Cd-QDs on conformational and functional changes of Gpx3, systematical measurements including calorimetric, multispectroscopic studies, and molecular model studies were carried out on molecular level. Results showed that Cd-QDs binds to Gpx3 via Van der Waals' force and hydrogen bonds, resulting in structural changes with increasing contents of α-helix. By interacting with Glu136 in the cavity of Gpx3 as well as Phe132, Pro130, and Van129 surrounded, Cd-QDs changes the microenvironment of fluorophore and further reduce the activity of Gpx3.

Keywords: Cd-QDs; glutathione peroxidase3; kidney toxicity; molecular mechanism; redox balance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cadmium
  • Cell Survival / drug effects
  • Glutathione Peroxidase / chemistry
  • Glutathione Peroxidase / metabolism*
  • Kidney / drug effects*
  • Kidney / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Docking Simulation
  • Oxidation-Reduction / drug effects
  • Primary Cell Culture
  • Quantum Dots / chemistry
  • Quantum Dots / toxicity*
  • Selenium

Substances

  • Cadmium
  • Glutathione Peroxidase
  • Selenium