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The Novel role of peroxiredoxin-2 in red cell membrane protein homeostasis and senescence

Matté , Alessandro and Pantaleo, Antonella and Ferru, Emanuela and Turrini, Franco and Bertoldi, Mariarita and Lupo, Francesca and Siciliano, Angela and Ho Zoon, Chae and De Franceschi, Lucia (2014) The Novel role of peroxiredoxin-2 in red cell membrane protein homeostasis and senescence. Free radical biology and medicine, Vol. 76 , p. 80-88. ISSN 0891-5849. eISSN 1873-4596. Article.

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DOI: 10.1016/j.freeradbiomed.2014.08.004

Abstract

Peroxiredoxin-2 (Prx2), a typical two-cysteine peroxiredoxin, is the third most abundant protein in red cells. Although progress has been made in the functional characterization of Prx2, its role in red cell membrane protein homeostasis is still under investigation. Here, we studied Prx2−/− mouse red cells. The absence of Prx2 promotes (i) activation of the oxidative-induced Syk pathway; (ii) increased band 3 Tyr phosphorylation, with clustered band 3; and (iii) increased heat shock protein (HSP27 and HSP70) membrane translocation. This was associated with enhanced in vitro erythrophagocytosis of Prx2−/− red cells and reduced Prx2−/− red cell survival, indicating the possible role of Prx2 membrane recruitment in red cell aging and in the clearance of oxidized hemoglobin and damaged proteins through microparticles. Indeed, we observed an increased release of microparticles from Prx2−/− mouse red cells. The mass spectrometric analysis of erythroid microparticles found hemoglobin chains, membrane proteins, and HSPs. To test these findings, we treated Prx2−/− mice with antioxidants in vivo. We observed that N-acetylcysteine reduced (i) Syk activation, (ii) band 3 clusterization, (iii) HSP27 membrane association, and (iv) erythroid microparticle release, resulting in increased Prx2−/− mouse red cell survival. Thus, we propose that Prx2 may play a cytoprotective role in red cell membrane protein homeostasis and senescence.

Item Type:Article
ID Code:10613
Status:Published
Refereed:Yes
Uncontrolled Keywords:Peroxiredoxin-2, red cells, N-acetylcysteine, oxidative stress, microparticles, free radicals
Subjects:Area 05 - Scienze biologiche > BIO/09 Fisiologia
Divisions:001 Università di Sassari > 01-a Nuovi Dipartimenti dal 2012 > Scienze Biomediche
Publisher:Elsevier
ISSN:0891-5849
eISSN:1873-4596
Deposited On:14 Jan 2015 10:42

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