title: Peroxiredoxin-2 expression is increased in beta-thalassemic mouse red cells but is displaced from the membrane as a marker of oxidative stress.
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 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.
authors.affiliation: Section of Internal Medicine, Department of Clinical and Experimental Medicine, University of Verona, 37134 Verona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Matte
authors.forename: Philip S
authors.initials: PS
authors.lastname: Low
authors.forename: Franco
authors.initials: F
authors.lastname: Turrini
authors.forename: Mariarita
authors.initials: M
authors.lastname: Bertoldi
authors.forename: Maria Estela
authors.initials: ME
authors.lastname: Campanella
authors.forename: Daniela
authors.initials: D
authors.lastname: Spano
authors.forename: Antonella
authors.initials: A
authors.lastname: Pantaleo
authors.forename: Angela
authors.initials: A
authors.lastname: Siciliano
authors.forename: Lucia
authors.initials: L
authors.lastname: De Franceschi
mesh_terms: D000818:Animals; D003958:Diamide / Q000494:pharmacology; D004195:Disease Models, Animal; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006420:Hemeproteins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000096:biosynthesis* / Q000097:blood; D010659:Phenylhydrazines / Q000494:pharmacology; D017086:beta-Thalassemia / Q000503:physiopathology*
chemical_list: D006420:Hemeproteins; D010659:Phenylhydrazines; C001332:hemichrome; C030299:phenylhydrazine; D003958:Diamide; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins