title: The novel role of peroxiredoxin-2 in red cell membrane protein homeostasis and senescence.
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.
authors.affiliation: Department of Medicine, Section of Internal Medicine, University of Verona, AOUI-Policlinico GB Rossi, 37134 Verona, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Matté
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Pantaleo
authors.affiliation: Department of Oncology, University of Torino, Torino, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ferru
authors.affiliation: Department of Oncology, University of Torino, Torino, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Turrini
authors.affiliation: 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.
authors.forename: Mariarita
authors.initials: M
authors.lastname: Bertoldi
authors.affiliation: Department of Medicine, Section of Internal Medicine, University of Verona, AOUI-Policlinico GB Rossi, 37134 Verona, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Lupo
authors.affiliation: Department of Medicine, Section of Internal Medicine, University of Verona, AOUI-Policlinico GB Rossi, 37134 Verona, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Siciliano
authors.affiliation: School of Biological Science and Technology, Chonnam National University, Gwangjiu, Korea.
authors.forename: Chae
authors.initials: C
authors.lastname: Ho Zoon
authors.affiliation: Department of Medicine, Section of Internal Medicine, University of Verona, AOUI-Policlinico GB Rossi, 37134 Verona, Italy. Electronic address: lucia.defranceschi@univr.it.
authors.forename: Lucia
authors.initials: L
authors.lastname: De Franceschi
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001457:Anion Exchange Protein 1, Erythrocyte / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival; D016922:Cellular Senescence; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism*; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015151:Immunoblotting; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D000072377:Syk Kinase
chemical_list: D001457:Anion Exchange Protein 1, Erythrocyte; D000975:Antioxidants; D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D018398:Homeodomain Proteins; C486699:Hspb2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D016877:Oxidants; C115469:Prrx2 protein, mouse; D006861:Hydrogen Peroxide; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D000111:Acetylcysteine
keywords: Free radicals; Microparticles; N-acetylcysteine; Oxidative stress; Peroxiredoxin-2; Red cells