{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:22:52Z","timestamp":1760145772605,"version":"build-2065373602"},"reference-count":82,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Bristol","award":["EP\/L016494\/1","WP-15-05","IS-BTU-1214-10032"],"award-info":[{"award-number":["EP\/L016494\/1","WP-15-05","IS-BTU-1214-10032"]}]},{"DOI":"10.13039\/100009033","name":"NHSBT R&amp;D","doi-asserted-by":"publisher","award":["EP\/L016494\/1","WP-15-05","IS-BTU-1214-10032"],"award-info":[{"award-number":["EP\/L016494\/1","WP-15-05","IS-BTU-1214-10032"]}],"id":[{"id":"10.13039\/100009033","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research Blood and Transplant Research Unit","doi-asserted-by":"publisher","award":["EP\/L016494\/1","WP-15-05","IS-BTU-1214-10032"],"award-info":[{"award-number":["EP\/L016494\/1","WP-15-05","IS-BTU-1214-10032"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>The regulation of reactive oxygen species (ROS) in red blood cells (RBCs) is crucial for maintaining functionality and lifespan. Indeed, dysregulated ROS occurs in haematological diseases such as sickle cell disease and \u03b2-thalassaemia. In order to combat this, RBCs possess high levels of protective antioxidant enzymes. We aimed to further boost RBC antioxidant capacity by overexpressing peroxiredoxin (Prxs) and glutathione peroxidase (GPxs) enzymes. Multiple antioxidant enzyme cDNAs were individually overexpressed in expanding immortalised erythroblasts using lentivirus, including Prx isoforms 1, 2, and 6 and GPx isoforms 1 and 4. Enhancing Prx protein expression proved straightforward, but GPx overexpression required modifications. For GPx4, these modifications included adding a SECIS element in the 3\u2019UTR, the removal of a mitochondrial-targeting sequence, and removing putative ubiquitination sites. Culture-derived reticulocytes exhibiting enhanced levels of Prx and GPx antioxidant proteins were successfully engineered, demonstrating a novel approach to improve RBC resilience to oxidative stress. Further work is needed to explore the activity of these proteins and their impact on RBC metabolism, but this strategy shows promise for improving RBC function in physiological and pathological contexts and during storage for transfusion. Enhancing the antioxidant capacity of reticulocytes has exciting promise for developing culture-derived RBCs with enhanced resistance to oxidative damage and offers new therapeutic interventions in diseases with elevated oxidative stress.<\/jats:p>","DOI":"10.3390\/antiox13091070","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T03:45:21Z","timestamp":1725248721000},"page":"1070","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Modulation of Antioxidant Enzyme Expression of In Vitro Culture-Derived Reticulocytes"],"prefix":"10.3390","volume":"13","author":[{"given":"Hannah D.","family":"Langlands","sequence":"first","affiliation":[{"name":"School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah K.","family":"Shoemark","sequence":"additional","affiliation":[{"name":"School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4395-9396","authenticated-orcid":false,"given":"Ashley M.","family":"Toye","sequence":"additional","affiliation":[{"name":"School of Biochemistry, University of Bristol, Biomedical Sciences Building, University Walk, Bristol BS8 1TD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mohanty, J.G., Nagababu, E., and Rifkind, J.M. (2014). Red Blood Cell Oxidative Stress Impairs Oxygen Delivery and Induces Red Blood Cell Aging. Front. Physiol., 5.","DOI":"10.3389\/fphys.2014.00084"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.redox.2015.07.018","article-title":"Oxidative Stress in \u03b2-Thalassaemia and Sickle Cell Disease","volume":"6","author":"Voskou","year":"2015","journal-title":"Redox Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/202607a0","article-title":"A Comparison of the Effect of Menadione, Methylene Blue and Ascorbic Acid on the Reduction of Meth\u00e6moglobin in Vivo","volume":"202","author":"Neumann","year":"1964","journal-title":"Nature."},{"key":"ref_4","first-page":"6960","article-title":"The Generation of Superoxide Radical during the Autoxidation of Hemoglobin","volume":"247","author":"Misra","year":"1972","journal-title":"J. Biochem."},{"key":"ref_5","first-page":"389","article-title":"Biochemistry of Red Cell Aging in Vivo and Storage Lesions","volume":"7","author":"Zolla","year":"2013","journal-title":"Eur. Hematol. Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1111\/j.1742-4658.2009.07472.x","article-title":"Biopreservation of Red Blood Cells\u2014The Struggle with Hemoglobin Oxidation","volume":"277","author":"Kanias","year":"2010","journal-title":"FEBS J."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Wang, Q., and Zennadi, R. (2021). The Role of RBC Oxidative Stress in Sickle Cell Disease: From the Molecular Basis to Pathologic Implications. Antioxidants, 10.","DOI":"10.3390\/antiox10101608"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/10715760600592962","article-title":"Age-Associated Analysis of Oxidative Stress Parameters in Human Plasma and Erythrocytes","volume":"40","author":"Gil","year":"2009","journal-title":"Free Radic. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"107","DOI":"10.3324\/haematol.2011.051789","article-title":"Time-Course Investigation of SAGM-Stored Leukocyte-Filtered Red Bood Cell Concentrates: From Metabolism to Proteomics","volume":"97","author":"Vaglio","year":"2012","journal-title":"Haematologica"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/j.1582-4934.2007.00008.x","article-title":"Progressive Oxidation of Cytoskeletal Proteins and Accumulation of Denatured Hemoglobin in Stored Red Cells","volume":"11","author":"Kriebardis","year":"2007","journal-title":"J. Cell Mol. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1943","DOI":"10.1111\/j.1537-2995.2008.01794.x","article-title":"RBC-Derived Vesicles during Storage: Ultrastructure, Protein Composition, Oxidation, and Signaling Components","volume":"48","author":"Kriebardis","year":"2008","journal-title":"Transfusion"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kozlova, E., Chernysh, A., Moroz, V., Sergunova, V., Gudkova, O., and Manchenko, E. (2017). Morphology, Membrane Nanostructure and Stiffness for Quality Assessment of Packed Red Blood Cells. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-08255-9"},{"key":"ref_13","first-page":"124","article-title":"Two-Step Process of Cytoskeletal Structural Damage during Long-Term Storage of Packed Red Blood Cells","volume":"19","author":"Kozlova","year":"2021","journal-title":"Blood Transfus."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Vona, R., Sposi, N.M., Mattia, L., Gambardella, L., Straface, E., and Pietraforte, D. (2021). Sickle Cell Disease: Role of Oxidative Stress and Antioxidant Therapy. Antioxidants, 10.","DOI":"10.3390\/antiox10020296"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.bbagen.2007.11.009","article-title":"N-Acetylcysteine Amide (AD4) Attenuates Oxidative Stress in Beta-Thalassemia Blood Cells","volume":"1780","author":"Amer","year":"2008","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1034\/j.1600-0609.2003.00011.x","article-title":"Flow Cytometric Measurement of Reactive Oxygen Species Production by Normal and Thalassaemic Red Blood Cells","volume":"70","author":"Amer","year":"2003","journal-title":"Eur. J. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3324\/haematol.2013.090076","article-title":"Resveratrol Accelerates Erythroid Maturation by Activation of FoxO3 and Ameliorates Anemia in Beta-Thalassemic Mice","volume":"99","author":"Franco","year":"2014","journal-title":"Haematologica"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/j.freeradbiomed.2010.05.003","article-title":"Peroxiredoxin-2 Expression Is Increased in \u03b2-Thalassemic Mouse Red Cells but Is Displaced from the Membrane as a Marker of Oxidative Stress","volume":"49","author":"Matte","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Melo, D., Coimbra, S., Rocha, S., and Santos-Silva, A. (2023). Inhibition of Erythrocyte\u2019s Catalase, Glutathione Peroxidase or Peroxiredoxin 2-Impact on Cytosol and Membrane. Arch. Biochem. Biophys., 739.","DOI":"10.1016\/j.abb.2023.109569"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1021\/bi00906a038","article-title":"Glutathione Peroxidase: The Primary Agent for the Elimination of Hydrogen Peroxide in Erythrocytes","volume":"2","author":"Cohen","year":"2002","journal-title":"Biochemistry"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1016\/j.freeradbiomed.2005.07.002","article-title":"Hemoglobin Autoxidation and Regulation of Endogenous H2O2 Levels in Erythrocytes","volume":"39","author":"Johnson","year":"2005","journal-title":"Free Radic. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.freeradbiomed.2009.11.021","article-title":"The Effects of Disruption of Genes for Peroxiredoxin-2, Glutathione Peroxidase-1, and Catalase on Erythrocyte Oxidative Metabolism","volume":"48","author":"Johnson","year":"2010","journal-title":"Free Radic. Biol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3289","DOI":"10.1016\/j.bbagen.2012.11.020","article-title":"Glutathione Peroxidases","volume":"1830","author":"Maiorino","year":"2013","journal-title":"Biochim. Et. Biophys. Acta (BBA) Gen. Subj."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.freeradbiomed.2018.09.014","article-title":"Role of GPX4 in Ferroptosis and Its Pharmacological Implication","volume":"133","author":"Seibt","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"van Vuren, A.J., van Beers, E.J., and van Wijk, R. (2021). A Proposed Concept for Defective Mitophagy Leading to Late Stage Ineffective Erythropoiesis in Pyruvate Kinase Deficiency. Front. Physiol., 11.","DOI":"10.3389\/fphys.2020.609103"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1182\/blood-2015-06-654194","article-title":"Glutathione Peroxidase 4 Prevents Necroptosis in Mouse Erythroid Precursors","volume":"127","author":"Canli","year":"2016","journal-title":"Blood"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"937","DOI":"10.3324\/haematol.2018.212977","article-title":"Glutathione Peroxidase 4 and Vitamin E Control Reticulocyte Maturation, Stress Erythropoiesis and Iron Homeostasis","volume":"105","author":"Altamura","year":"2020","journal-title":"Haematologica"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Rademacher, M., Kuhn, H., and Borchert, A. (2021). Expression Silencing of Glutathione Peroxidase 4 in Mouse Erythroleukemia Cells Delays In Vitro Erythropoiesis. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22157795"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"5666","DOI":"10.1182\/bloodadvances.2020003100","article-title":"A New Role of Glutathione Peroxidase 4 during Human Erythroblast Enucleation","volume":"4","author":"Messaoudi","year":"2020","journal-title":"Blood Adv."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"D917","DOI":"10.1093\/nar\/gkv1101","article-title":"BloodSpot: A Database of Gene Expression Profiles and Transcriptional Programs for Healthy and Malignant Haematopoiesis","volume":"44","author":"Bagger","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Sadowska-Bartosz, I., and Bartosz, G. (2023). Peroxiredoxin 2: An Important Element of the Antioxidant Defense of the Erythrocyte. Antioxidants, 12.","DOI":"10.3390\/antiox12051012"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/j.bbrc.2012.08.113","article-title":"Peroxiredoxin II Is Essential for Preventing Hemolytic Anemia from Oxidative Stress through Maintaining Hemoglobin Stability","volume":"426","author":"Han","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.2741\/4770","article-title":"Interactions between Human Hemoglobin Subunits and Peroxiredoxin 2","volume":"24","author":"Ma","year":"2019","journal-title":"Front. Biosci. Landmark"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1046\/j.1432-1033.2003.03393.x","article-title":"Antioxidant Protein 2 Prevents Methemoglobin Formation in Erythrocyte Hemolysates","volume":"270","author":"Stuhlmeier","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Melo, D., Ribeiro, S., Santos-Silva, A., and Rocha, S. (2018). Role of Peroxiredoxin 2 in Erythrocyte Antioxidant Defense: Peroxidase and Chaperone. Free Radic. Biol. Med., 120.","DOI":"10.1016\/j.freeradbiomed.2018.04.274"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6944","DOI":"10.1021\/bi000034j","article-title":"Interaction of Human Thiol-Specific Antioxidant Protein 1 with Erythrocyte Plasma Membrane","volume":"39","author":"Cha","year":"2000","journal-title":"Biochemistry"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Rocha, S., Rocha-Pereira, P., Cleto, E., Ferreira, F., Belo, L., and Santos-Silva, A. (2020). Linkage of Typically Cytosolic Peroxidases to Erythrocyte Membrane\u2014A Possible Mechanism of Protection in Hereditary Spherocytosis. Biochim. Et. Biophys. Acta (BBA) Biomembr., 1862.","DOI":"10.1016\/j.bbamem.2019.183172"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.freeradbiomed.2012.10.543","article-title":"Membrane Association of Peroxiredoxin-2 in Red Cells Is Mediated by the N-Terminal Cytoplasmic Domain of Band 3","volume":"55","author":"Matte","year":"2013","journal-title":"Free Radic. Biol. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.bcmd.2009.03.002","article-title":"Linkage of Cytosolic Peroxiredoxin 2 to Erythrocyte Membrane Imposed by Hydrogen Peroxide-Induced Oxidative Stress","volume":"43","author":"Rocha","year":"2009","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.abb.2016.12.003","article-title":"Peroxiredoxin 6 in the Repair of Peroxidized Cell Membranes and Cell Signaling","volume":"617","author":"Fisher","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1111\/trf.13039","article-title":"Accumulation of Oxidized Peroxiredoxin 2 in Red Blood Cells and Its Prevention","volume":"55","author":"Bayer","year":"2015","journal-title":"Transfusion"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1111\/j.1537-2995.2010.03026.x","article-title":"The Effects of Long-Term Storage of Human Red Blood Cells on the Glutathione Synthesis Rate and Steady-State Concentration","volume":"51","author":"Whillier","year":"2011","journal-title":"Transfusion"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1182\/blood-2021-153836","article-title":"An Ex Vivo Model of Oxidatively Stressed Red Blood Cells Demonstrates a Role for Exogenous Amino Acids in Enhancing Red Blood Cell Function and Morphology","volume":"138","author":"Colvin","year":"2021","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Pearson, A.G., Pullar, J.M., Cook, J., Spencer, E.S., Vissers, M.C., Carr, A.C., and Hampton, M.B. (2021). Peroxiredoxin 2 Oxidation Reveals Hydrogen Peroxide Generation within Erythrocytes during High-Dose Vitamin C Administration. Redox Biol., 43.","DOI":"10.1016\/j.redox.2021.101980"},{"key":"ref_45","first-page":"376","article-title":"Storing Red Blood Cells with Vitamin C and N-Acetylcysteine Prevents Oxidative Stress-Related Lesions: A Metabolomics Overview","volume":"12","author":"Pallotta","year":"2014","journal-title":"Blood Transfus."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"961049","DOI":"10.1155\/2015\/961049","article-title":"Prospects of Vitamin C as an Additive in Plasma of Stored Blood","volume":"2015","author":"Vani","year":"2015","journal-title":"Adv. Hematol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1080\/10715760000301061","article-title":"Glutathione Loading Prevents Free Radical Injury in Red Blood Cells after Storage","volume":"33","author":"Dumaswala","year":"2000","journal-title":"Free Radic. Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.3109\/09553002.2013.877173","article-title":"A Moderate Protective Effect of Quercetin against \u03b3-Irradiation- and Storage-Induced Oxidative Damage in Red Blood Cells for Transfusion","volume":"90","author":"Zbikowska","year":"2014","journal-title":"Int. J. Radiat. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"7556219","DOI":"10.1155\/2022\/7556219","article-title":"Erythrocyte Storage Lesion Improvements Mediated by Naringin Screened from Vegetable\/Fruit Juice Using Cell Extract and HPLC-MS","volume":"2022","author":"She","year":"2022","journal-title":"J. Anal. Methods Chem."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.abb.2017.02.012","article-title":"N-Acetylcysteine Improves the Quality of Red Blood Cells Stored for Transfusion","volume":"621","author":"Amen","year":"2017","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Nemkov, T., Yoshida, T., Nikulina, M., and D\u2019Alessandro, A. (2022). High-Throughput Metabolomics Platform for the Rapid Data-Driven Development of Novel Additive Solutions for Blood Storage. Front. Physiol., 13.","DOI":"10.3389\/fphys.2022.833242"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1111\/j.1537-2995.2008.02038.x","article-title":"Anaerobic Storage of Red Blood Cells in a Novel Additive Solution Improves in Vivo Recovery","volume":"49","author":"Dumont","year":"2009","journal-title":"Transfusion"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1111\/trf.13364","article-title":"CO2-Dependent Metabolic Modulation in Red Blood Cells Stored under Anaerobic Conditions","volume":"56","author":"Dumont","year":"2016","journal-title":"Transfusion"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1423-0410.2007.00915.x","article-title":"Storage of Red Blood Cells under Anaerobic Conditions","volume":"93","author":"Hess","year":"2007","journal-title":"Vox Sang."},{"key":"ref_55","first-page":"172","article-title":"Enhancing Uniformity and Overall Quality of Red Cell Concentrate with Anaerobic Storage","volume":"15","author":"Yoshida","year":"2017","journal-title":"Blood Transfus."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"256","DOI":"10.4103\/jehp.jehp_1638_20","article-title":"Dose-Dependent Efficacy of Antioxidant Nanoparticles on Red Blood Cells Storage","volume":"10","author":"Barzegar","year":"2021","journal-title":"J. Educ. Health Promot."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1021\/acschembio.0c00309","article-title":"Modulation of Redox Signaling and Thiol Homeostasis in Red Blood Cells by Peroxiredoxin Mimetics","volume":"15","author":"Chakrabarty","year":"2020","journal-title":"ACS Chem. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.bcmd.2011.01.002","article-title":"Assessment of Oxidative Stress in Patients with Sickle Cell Disease: The Glutathione System and the Oxidant\u2013Antioxidant Status","volume":"46","author":"Gizi","year":"2011","journal-title":"Blood Cells Mol. Dis."},{"key":"ref_59","first-page":"897","article-title":"Blood Antioxidant Parameters in Sickle Cell Anemia Patients in Steady State","volume":"100","author":"Manfredini","year":"2008","journal-title":"J. Natl. Med. Assoc."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Romanello, K.S., Teixeira, K.K.L., Silva, J.P.M.O., Nagamatsu, S.T., Bezerra, M.A.C., Domingos, I.F., Martins, D.A.P., Araujo, A.S., Lanaro, C., and Breyer, C.A. (2018). Global Analysis of Erythroid Cells Redox Status Reveals the Involvement of Prdx1 and Prdx2 in the Severity of Beta Thalassemia. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0208316"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1089\/ars.2014.6237","article-title":"The Interplay Between Peroxiredoxin-2 and Nuclear Factor-Erythroid 2 Is Important in Limiting Oxidative Mediated Dysfunction in \u03b2-Thalassemic Erythropoiesis","volume":"23","author":"Matte","year":"2015","journal-title":"Antioxid. Redox Signal"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1595","DOI":"10.3324\/haematol.2011.043612","article-title":"Oxidative Stress Modulates Heme Synthesis and Induces Peroxiredoxin-2 as a Novel Cytoprotective Response in \u03b2-Thalassemic Erythropoiesis","volume":"96","author":"Bertoldi","year":"2011","journal-title":"Haematologica"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1002\/prca.201600086","article-title":"Analysis of Protein Profiling Studies of \u03b2-Thalassemia\/Hb E Disease","volume":"10","author":"Lithanatudom","year":"2016","journal-title":"Proteom. Clin. Appl."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"112","DOI":"10.3324\/haematol.2020.273946","article-title":"Beta Thalassemia Minor Is a Beneficial Determinant of Red Blood Cell Storage Lesion","volume":"107","author":"Tzounakas","year":"2022","journal-title":"Haematologica"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Anastasiadi, A.T., Paronis, E.C., Arvaniti, V.Z., Velentzas, A.D., Apostolidou, A.C., Balafas, E.G., Dzieciatkowska, M., Kostomitsopoulos, N.G., Stamoulis, K., and Papassideri, I.S. (2021). The Post-Storage Performance of RBCs from Beta-Thalassemia Trait Donors Is Related to Their Storability Profile. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222212281"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Stolwijk, J.M., Stefely, J.A., Veling, M.T., van \u2018t Erve, T.J., Wagner, B.A., Raife, T.J., and Buettner, G.R. (2021). Red Blood Cells Contain Enzymatically Active GPx4 Whose Abundance Anticorrelates with Hemolysis during Blood Bank Storage. Redox Biol., 46.","DOI":"10.1016\/j.redox.2021.102073"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e146077","DOI":"10.1172\/JCI146077","article-title":"Multiple-Ancestry Genome-Wide Association Study Identifies 27 Loci Associated with Measures of Hemolysis Following Blood Storage","volume":"131","author":"Page","year":"2021","journal-title":"J. Clin. Invest."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"822","DOI":"10.1016\/j.omtm.2020.03.029","article-title":"Expression and Retention of Thymidine Phosphorylase in Cultured Reticulocytes as a Novel Treatment for MNGIE","volume":"17","author":"Meinders","year":"2020","journal-title":"Mol. Ther. Methods Clin. Dev."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"14750","DOI":"10.1038\/ncomms14750","article-title":"An Immortalized Adult Human Erythroid Line Facilitates Sustainable and Scalable Generation of Functional Red Cells","volume":"8","author":"Trakarnsanga","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"D512","DOI":"10.1093\/nar\/gku1267","article-title":"PhosphoSitePlus, 2014: Mutations, PTMs and Recalibrations","volume":"43","author":"Hornbeck","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.1002\/jcc.20084","article-title":"UCSF Chimera--a Visualization System for Exploratory Research and Analysis","volume":"25","author":"Pettersen","year":"2004","journal-title":"J Comput Chem."},{"key":"ref_72","unstructured":"(2024, August 14). BLAST: Basic Local Alignment Search Tool, Available online: https:\/\/blast.ncbi.nlm.nih.gov\/Blast.cgi."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1002\/jcc.20291","article-title":"GROMACS: Fast, Flexible, and Free","volume":"26","author":"Lindahl","year":"2005","journal-title":"J Comput Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1107\/S0021889892009944","article-title":"PROCHECK: A Program to Check the Stereo-chemical Quality of Protein Structures","volume":"26","author":"Laskowski","year":"1993","journal-title":"J. Appl. Crystallogr."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"5472","DOI":"10.1021\/bi400462j","article-title":"Selenocysteine Confers Resistance to Inactivation by Oxidation in Thioredoxin Reductase: Comparison of Selenium and Sulfur Enzymes","volume":"52","author":"Snider","year":"2013","journal-title":"Biochemistry"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1096\/fj.10-177147","article-title":"Cysteine Mutant of Mammalian GPx4 Rescues Cell Death Induced by Disruption of the Wild-Type Selenoenzyme","volume":"25","author":"Mannes","year":"2011","journal-title":"FASEB J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"eaan0218","DOI":"10.1126\/science.aan0218","article-title":"UBE2O Remodels the Proteome during Terminal Erythroid Differentiation","volume":"357","author":"Nguyen","year":"2017","journal-title":"Science"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1073\/pnas.1819728116","article-title":"Chaperone-Mediated Autophagy Is Involved in the Execution of Ferroptosis","volume":"116","author":"Wu","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1515\/hsz-2020-0286","article-title":"Emerging Roles for Non-Selenium Containing ER-Resident Glutathione Peroxidases in Cell Signaling and Disease","volume":"402","author":"Buday","year":"2021","journal-title":"Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"681","DOI":"10.4161\/rna.20147","article-title":"The Differential Expression of Glutathione Peroxidase 1 and 4 Depends on the Nature of the SECIS Element","volume":"9","author":"Duhieu","year":"2012","journal-title":"RNA Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1182\/bloodadvances.2018023515","article-title":"Absolute Proteome Quantification of Highly Purified Populations of Circulating Reticulocytes and Mature Erythrocytes","volume":"2","author":"Gautier","year":"2018","journal-title":"Blood Adv."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1470","DOI":"10.1016\/j.celrep.2016.06.085","article-title":"Comprehensive Proteomic Analysis of Human Erythropoiesis","volume":"16","author":"Gautier","year":"2016","journal-title":"Cell Rep."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/9\/1070\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:46:58Z","timestamp":1760111218000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/13\/9\/1070"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,2]]},"references-count":82,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2024,9]]}},"alternative-id":["antiox13091070"],"URL":"https:\/\/doi.org\/10.3390\/antiox13091070","relation":{},"ISSN":["2076-3921"],"issn-type":[{"type":"electronic","value":"2076-3921"}],"subject":[],"published":{"date-parts":[[2024,9,2]]}}}