The concentration of extracellular superoxide dismutase in plasma is maintained by LRP-mediated endocytosis

Free Radic Biol Med. 2010 Sep 1;49(5):894-9. doi: 10.1016/j.freeradbiomed.2010.06.019. Epub 2010 Jun 27.


In this study, we show that human extracellular superoxide dismutase (EC-SOD) binds to low-density lipoprotein receptor-related protein (LRP). This interaction is most likely responsible for the removal of EC-SOD from the blood circulation via LRP expressed in liver tissue. The receptor recognition site was located within the extracellular matrix-binding region of EC-SOD. This region encompasses the naturally occurring Arg213Gly amino acid substitution, which affects the affinity of EC-SOD for ligands in the extracellular space. Interestingly, the binding between LRP and Arg213Gly EC-SOD was significantly reduced, thus clarifying the observation that hetero- or homozygous carriers present with a significant increase in EC-SOD in their blood. On the basis of our results, we speculate that EC-SOD synthesized locally in tissues diffuses slowly into the circulation, from where it is removed by binding to LRP present in the liver. The interaction between LRP and EC-SOD is thus likely to be important for maintaining redox balance in the circulation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Endocytosis / genetics
  • Endocytosis / physiology*
  • Female
  • Hep G2 Cells
  • Humans
  • Low Density Lipoprotein Receptor-Related Protein-1 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-1 / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-1 / physiology*
  • Metabolic Clearance Rate
  • Mice
  • Osmolar Concentration
  • Oxidation-Reduction
  • Protein Binding / physiology
  • Superoxide Dismutase / blood*
  • Superoxide Dismutase / chemistry
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*


  • Low Density Lipoprotein Receptor-Related Protein-1
  • SOD3 protein, human
  • Superoxide Dismutase