The concentration of extracellular superoxide dismutase in plasma is maintained by LRP-mediated endocytosis.
The concentration of extracellular superoxide dismutase in plasma is maintained by LRP-mediated endocytosis.
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血浆中细胞外超氧化物歧化酶的浓度由 LRP 介导的内吞作用维持。
DOI：
10.1016/j.freeradbiomed.2010.06.019
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发表时间：
2010
影响因子：
7.4
通讯作者：
Enghild,JanJ
中科院分区：
文献类型：
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作者：
Petersen,SteenV;Thogersen,IdaB;Valnickova,Zuzana;Nielsen,MortenS;Petersen,JaneS;Poulsen,EbbeT;Jacobsen,Christian;Oury,TimD;Moestrup,SorenK;Crapo,JamesD;Nielsen,NielsChr;Kristensen,Torsten;Enghild,JanJ
在这项研究中，我们表明，人细胞外超氧化物歧化酶（EC-SOD）结合低密度脂蛋白受体相关蛋白（LRP）。这种相互作用很可能是通过肝组织中表达的LRP从血液循环中去除EC-SOD的原因。受体识别位点位于EC-SOD的细胞外基质结合区。该区域包括天然存在的Arg 213 Gly氨基酸取代，其影响EC-SOD对细胞外空间中配体的亲和力。有趣的是，LRP和Arg 213 Gly EC-SOD之间的结合显著降低，从而澄清了杂合或纯合携带者血液中EC-SOD显著增加的观察结果。我们的研究结果的基础上，我们推测，EC-SOD在组织中合成的局部扩散缓慢进入循环，从那里它是通过结合到LRP存在于肝脏中删除。因此，LRP和EC-SOD之间的相互作用可能对维持循环中的氧化还原平衡很重要。
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.