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

Alessandro Matte, Philip S. Low, Franco Turrini, Mariarita Bertoldi, Maria Estela Campanella, Daniela Spano, Antonella Pantaleo, Angela Siciliano, Lucia De Franceschi

Research output: Contribution to journalArticle

43 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)457-466
Number of pages10
JournalFree Radical Biology and Medicine
Volume49
Issue number3
DOIs
StatePublished - Aug 2010

Keywords

  • Diamide
  • Erythrocytes
  • Free radicals
  • Hydrogen peroxide
  • Oxidative damage
  • Phenylhydrazine
  • Thalassemias

ASJC Scopus subject areas

  • Biochemistry
  • Physiology (medical)

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