Interactions between peroxiredoxin 2, hemichrome and the erythrocyte membrane
Interactions between peroxiredoxin 2, hemichrome and the erythrocyte membrane
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DOI：
10.1080/10715762.2016.1241995
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发表时间：
2016-12-01
影响因子：
3.3
通讯作者：
Winterbourn, Christine C.
中科院分区：
文献类型：
--
作者：
Bayer, Simone B.;Low, Felicia M.;Winterbourn, Christine C.
过氧化还蛋白2(Prx2)是红细胞中一种丰富的抗氧化蛋白质，可预防因血红蛋白氧化和亨氏小体形成而引起的溶血性贫血。一小部分Prx2与细胞膜结合，但结合的机制和相关性尚不清楚。我们研究了Prx2与红细胞膜和氧化血红蛋白的相互作用，以及这些相互作用是否依赖于Prx2的氧化还原状态。红细胞膜上Prx2的结合在过氧化氢处理后降低，但纯化的Prx2和分离的幽灵的研究表明，这种相互作用不依赖于Prx2的氧化还原状态。血红蛋白氧化会导致半染色质的形成，这是一种变性形式的蛋白质，作为衰老过程的一部分，它与细胞膜上的Band3蛋白结合，是亨氏小体的前身。半铬与Prx2竞争并减少Prx2与膜的结合，这可能解释了氧化剂暴露的细胞结合减少的原因。随着细胞内钙离子的增加，Prx2的膜结合增加，对H_2O_2或半铬不敏感，这表明了一种替代的结合模式。Prx2还通过延缓预先形成的半铬沉淀而显示出类似伴侣的活性。我们的结果表明，Prx2通过限制半染色质的膜结合，可以阻止Band3的聚集和衰老抗原的暴露。这一机制，加上观察到的氧化血红蛋白的伴侣活性，可能有助于预防溶血性贫血。
Peroxiredoxin 2 (Prx2) is an abundant antioxidant protein in erythrocytes that protects against hemolytic anemia resulting from hemoglobin oxidation and Heinz body formation. A small fraction of Prx2 is bound to the cell membrane, but the mechanism and relevance of binding are not clear. We have investigated Prx2 interactions with the erythrocyte membrane and oxidized hemoglobin and whether these interactions are dependent on Prx2 redox state. Membrane binding of Prx2 in erythrocytes decreased when the cells were treated with H2O2, but studies with purified Prx2 and isolated ghosts showed that the interaction was independent of Prx2 redox state. Hemoglobin oxidation leads to the formation of hemichrome, a denatured form of the protein that binds to Band3 protein in the cell membrane as part of the senescence process and is a precursor of Heinz bodies. Hemichrome competed with Prx2 and decreased Prx2 binding to the membrane, potentially explaining the decreased binding in oxidant-exposed cells. The increased membrane binding of Prx2 seen with increasing intracellular calcium was less sensitive to H2O2 or hemichrome, suggesting an alternative mode of binding. Prx2 was also shown to exhibit chaperone-like activity by retarding the precipitation of pre-formed hemichrome. Our results suggest that Prx2, by restricting membrane binding of hemichrome, could impede Band3 clustering and exposure of senescence antigens. This mechanism, plus the observed chaperone activity for oxidized hemoglobin, may help protect against hemolytic anemia.