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Free Radic Biol Med. 2014 Nov;76:80-8. doi: 10.1016/j.freeradbiomed.2014.08.004. Epub 2014 Aug 21.

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

Author information

1
Department of Medicine, Section of Internal Medicine, University of Verona, AOUI-Policlinico GB Rossi, 37134 Verona, Italy.
2
Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
3
Department of Oncology, University of Torino, Torino, Italy.
4
Department of Oncology, University of Torino, Torino, Italy; Department of Life and Reproduction Sciences, Section of Biochemistry, University of Verona, AOUI-Policlinico GB Rossi, 37134 Verona, Italy.
5
School of Biological Science and Technology, Chonnam National University, Gwangjiu, Korea.
6
Department of Medicine, Section of Internal Medicine, University of Verona, AOUI-Policlinico GB Rossi, 37134 Verona, Italy. Electronic address: lucia.defranceschi@univr.it.

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.

KEYWORDS:

Free radicals; Microparticles; N-acetylcysteine; Oxidative stress; Peroxiredoxin-2; Red cells

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