The novel role of peroxiredoxin-2 in red cell membrane protein homeostasis and senescence |
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| Institution: | 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 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;1. Department of Blood Cell Research, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;2. Department of Intensive Care Medicine, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands;3. Laboratory of Experimental Intensive Care and Anesthesia, Amsterdam University Medical Centers, location AMC, Amsterdam, The Netherlands;4. Department of Anesthesiology, University Medical Center Utrecht, Utrecht, The Netherlands;5. Department of Anesthesiology, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, The Netherlands;6. Department of Clinical Pathology, Suez Canal University, Ismailia, Egypt;7. Department of Product and Process Development, Sanquin Blood Bank, Amsterdam, The Netherlands;8. Department of Biochemistry and Molecular Genetics, University of Colorado Denver, Denver, CO;1. Atherothrombosis and Vascular Biology Laboratory, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia;2. Competence Cluster of Nutrition and Cardiovascular Health (nutriCARD), Jena-Halle-Leipzig, Germany;3. Department of Nutritional Biochemistry and Physiology, Institute of Nutrition, Friedrich Schiller University Jena, Jena, Germany;4. Institute of Human Genetics, University Medical Center Goettingen, Göttingen, Germany;5. Department of Nutritional, Food and Consumer Science, University of Applied Sciences Fulda, Fulda, Germany;6. Department of Pharmaceutical/Medicinal Chemistry, Institute of Pharmacy, Friedrich Schiller University Jena, Jena, Germany;7. Central Clinical School, Monash University, Melbourne, Australia;1. Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal;2. Institute for Interdisciplinary Research, University of Coimbra, 3030-789 Coimbra, Portugal;3. Departamento de Química e Bioquímica and Centro de Química e Bioquímica, Faculdade de Ciências, Universidade de Lisboa, Lisboa, Portugal;4. Coimbra Chemistry Center, University of Coimbra, 3004-535 Coimbra, Portugal |
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| 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. |
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| Keywords: | Peroxiredoxin-2 Red cells Oxidative stress Microparticles Free radicals |
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