Section of Internal Medicine, Department of Clinical and Experimental Medicine, University of Verona, 37134 Verona, Italy.
Free Radic Biol Med. 2010 Aug 1;49(3):457-66. doi: 10.1016/j.freeradbiomed.2010.05.003. Epub 2010 May 19.
Peroxiredoxin 2 (Prx2), the third most abundant cytoplasmic protein in red blood cells (RBCs), is involved in the defense against oxidative stress. Although much is known about Prx2 in healthy RBCs, its role in pathological RBCs remains largely unexplored. Here, we show that the expression and net content of Prx2 are markedly increased in RBCs from two mouse models of beta-thalassemia (beta-thal; Hbb(th/th) and Hbb(th3/+) strains). We also demonstrate that the increased expression of Prx2 correlates with the severity of the disease and that the amount of Prx2 bound to the membrane is markedly reduced in beta-thal mouse RBCs. To explore the impact of oxidative stress on Prx2 membrane association, we examined Prx2 dimerization and membrane translocation in murine RBCs exposed to various oxidants (phenylhydrazine, PHZ; diamide; H(2)O(2)). PHZ-treated RBCs, which mimic the membrane damage in beta-thal RBCs, exhibited a kinetic correlation among Prx2 membrane displacement, intracellular methemoglobin levels, and hemichrome membrane association, suggesting the possible masking of Prx2 docking sites by membrane-bound hemichromes, providing a possible mechanism for the accumulation of oxidized/dimerized Prx2 in the cytoplasm and the increased membrane damage in beta-thal RBCs. Thus, reduced access of Prx2 to the membrane in beta-thal RBCs represents a new factor that could contribute to the oxidative damage characterizing the pathology.
过氧化物酶 2（Prx2）是红细胞（RBC）中第三丰富的细胞质蛋白，参与抵抗氧化应激。尽管人们对健康 RBC 中的 Prx2 了解很多，但它在病理 RBC 中的作用在很大程度上仍未得到探索。在这里，我们表明，β-地中海贫血（β-地中海贫血；Hbb(th/th)和 Hbb(th3/+)品系）两种小鼠模型的 RBC 中 Prx2 的表达和净含量显着增加。我们还证明，Prx2 的表达增加与疾病的严重程度相关，并且β-地中海贫血小鼠 RBC 中与膜结合的 Prx2 量显着减少。为了探讨氧化应激对 Prx2 膜结合的影响，我们研究了暴露于各种氧化剂（苯肼，PHZ；二酰胺；H（2）O（2））的鼠 RBC 中 Prx2 的二聚化和膜易位。PHZ 处理的 RBC 模拟了β-地中海贫血 RBC 中的膜损伤，Prx2 膜位移、细胞内高铁血红蛋白水平和血红素膜结合之间存在动力学相关性，表明膜结合血红素可能掩盖 Prx2 对接位点，为氧化/二聚化 Prx2 在细胞质中的积累和β-地中海贫血 RBC 中膜损伤增加提供了一种可能的机制。因此，β-地中海贫血 RBC 中 Prx2 对膜的低亲和力代表了一种新的因素，可能有助于病理特征的氧化损伤。
