The cellular distribution of extracellular superoxide dismutase in macrophages is altered by cellular activation but unaffected by the naturally occurring R213G substitution
The cellular distribution of extracellular superoxide dismutase in macrophages is altered by cellular activation but unaffected by the naturally occurring R213G substitution
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DOI：
10.1016/j.freeradbiomed.2014.01.038
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发表时间：
2014-04-01
影响因子：
7.4
通讯作者：
Petersen, Steen V.
中科院分区：
文献类型：
--
作者：
Gottfredsen, Randi H.;Goldstrohm, David A.;Petersen, Steen V.
细胞外超氧化物歧化酶（EC-SOD）负责细胞外空间中产生的超氧化物自由基的歧化，并且已知由炎性细胞（包括巨噬细胞和嗜中性粒细胞）表达。在这里，我们表明，EC-SOD是由静息巨噬细胞和相关的细胞表面通过细胞外基质（ECM）结合区。在脂多糖诱导的细胞活化后，EC-SOD被重新定位并在细胞培养基和脂筏结构中检测到。虽然分泌的材料提出了一个显着降低配体结合能力，这可能是不相关的ECM结合区域的蛋白水解去除，因为从介质中回收的材料的完整性是可比的细胞表面相关蛋白。已知位于EC-SOD的ECM结合区的天然存在的R213 G氨基酸取代影响蛋白质的结合特性。然而，对表达R213 G EC-SOD的巨噬细胞的分析并未提供改变细胞分布的证据。我们的研究结果表明，EC-SOD在活化的巨噬细胞的炎症反应中起着动态的作用。(c)2014爱思唯尔公司All rights reserved.
Extracellular superoxide dismutase (EC-SOD) is responsible for the dismutation of the superoxide radical produced in the extracellular space and known to be expressed by inflammatory cells, including macrophages and neutrophils. Here we show that EC-SOD is produced by resting macrophages and associated with the cell surface via the extracellular matrix (ECM)-binding region. Upon cellular activation induced by lipopolysaccharide, EC-SOD is relocated and detected both in the cell culture medium and in lipid raft structures. Although the secreted material presented a significantly reduced ligand-binding capacity, this could not be correlated to proteolytic removal of the ECM-binding region, because the integrity of the material recovered from the medium was comparable to that of the cell surface-associated protein. The naturally occurring R213G amino acid substitution located in the ECM-binding region of EC-SOD is known to affect the binding characteristics of the protein. However, the analysis of macrophages expressing R213G EC-SOD did not present evidence of an altered cellular distribution. Our results suggest that EC-SOD plays a dynamic role in the inflammatory response mounted by activated macrophages. (c) 2014 Elsevier Inc. All rights reserved.