Peroxiredoxin-2 (Prx2) expression is increased in beta thalassemic mouse red cells but displaced from the membrane as marker of oxidative stress

Peroxiredoxin 2 (Prx2), the third most abundant cytoplasmic protein in red blood cells (RBCs), is involved in defence against oxidative-stress. Although much is known on 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 (Hbb(th/th), Hbb(th3/+)-strains; beta-thal). 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 (MetHb) levels and hemichromes 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 beta-thal-RBCs increased membrane damage. 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.