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

被引：15
作者：
Petersen, Steen V. [1 ,2 ,3 ]
Thogersen, Ida B. [1 ,2 ]
Valnickova, Zuzana [1 ,2 ]
Nielsen, Morten S. [3 ]
Petersen, Jane S. [1 ,2 ]
Poulsen, Ebbe T. [1 ,2 ]
Jacobsen, Christian [3 ]
Oury, Tim D. [4 ]
Moestrup, Soren K. [3 ]
Crapo, James D. [5 ]
Nielsen, Niels Chr. [2 ,6 ]
Kristensen, Torsten [1 ,2 ]
Enghild, Jan J. [1 ,2 ]
机构：
[1] Aarhus Univ, Dept Mol Biol, Ctr Insoluble Prot Struct, DK-8000 Aarhus C, Denmark
[2] Aarhus Univ, Interdisciplinary Nanosci Ctr, DK-8000 Aarhus C, Denmark
[3] Aarhus Univ, Dept Med Biochem, DK-8000 Aarhus C, Denmark
[4] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15260 USA
[5] Natl Jewish Med & Res Ctr, Dept Med, Denver, CO 80206 USA
[6] Aarhus Univ, Dept Chem, Ctr Insoluble Prot Struct, DK-8000 Aarhus C, Denmark
来源：
FREE RADICAL BIOLOGY AND MEDICINE | 2010年 / 49卷 / 05期
基金：
新加坡国家研究基金会; 美国国家卫生研究院;
关键词：
Antioxidant; Extracellular superoxide dismutase; Endocytosis; LDL receptor-related protein; Redox homeostasis; Free radicals; RECEPTOR-RELATED PROTEIN; HEPARIN-BINDING DOMAIN; EC-SOD; HUMAN ALPHA-2-MACROGLOBULIN; SULFATE PROTEOGLYCANS; CELL-SURFACE; OXIDATIVE FRAGMENTATION; ALPHA-MACROGLOBULINS; ENDOTHELIAL-CELLS; VASCULAR SYSTEM;
D O I：
10.1016/j.freeradbiomed.2010.06.019
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 (C) 2010 Elsevier Inc All rights reserved
引用
收藏
页码：894 / 899
页数：6
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