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Peroxiredoxin-2 expression is increased in β-thalassemic mouse red cells but is displaced from the membrane as a marker of oxidative stress

Mattè, Alessadro and Low, Philip S. and Turrini, Francesco Michelangelo and Bertoldi, Mariarita and Campanella, Maria Estela and Spano, Daniela and Pantaleo, Antonella and Siciliano, Angela and De Franceshi , Lucia (2010) Peroxiredoxin-2 expression is increased in β-thalassemic mouse red cells but is displaced from the membrane as a marker of oxidative stress. Free Radical Biology and Medicine, Vol. 49 (3), p. 457-466. eISSN 1873-4596. Article.

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DOI: 10.1016/j.freeradbiomed.2010.05.003

Abstract

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 β-thalassemia (β-thal; Hbbth/th and Hbbth3/+ 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 β-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; H2O2). PHZ-treated RBCs, which mimic the membrane damage in β-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 β-thal RBCs. Thus, reduced access of Prx2 to the membrane in β-thal RBCs represents a new factor that could contribute to the oxidative damage characterizing the pathology.

Item Type:Article
ID Code:5603
Status:Published
Refereed:Yes
Uncontrolled Keywords:Oxidative damage, diamide, phenylhydrazine, thalassemias, erythrocytes, hydrogen peroxide, free radicals
Subjects:Area 06 - Scienze mediche > MED/09 Medicina interna
Divisions:002 Altri enti e centri di ricerca del Nord Sardegna > Nurex Bioresearch Sassari, Sassari
Publisher:Elsevier
eISSN:1873-4596
Deposited On:11 Mar 2011 09:55

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