The concentration of extracellular superoxide dismutase in plasma is maintained by LRP-mediated endocytosis.
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.
Petersen, SV; Thøgersen, IB; Valnickova, Z; Nielsen, MS; Petersen, JS; Poulsen, ET; Jacobsen, C; Oury, TD; Moestrup, SK; Crapo, JD; Nielsen, NC; Kristensen, T; Enghild, JJ
Volume / Issue
Start / End Page
Pubmed Central ID
Electronic International Standard Serial Number (EISSN)
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)