{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:02:53Z","timestamp":1790870573364,"version":"4.1.0"},"reference-count":87,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T00:00:00Z","timestamp":1739404800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>\u03b2-thalassemia, a hereditary hemoglobinopathy, is caused by reduced or absent synthesis of the \u03b2-globin chains of hemoglobin. Three clinical conditions are recognized: \u03b2-thalassemia major, \u03b2-thalassemia intermedia, and \u03b2-thalassemia minor (\u03b2-Thal+). This latter condition occurs when an individual inherits a mutated \u03b2-globin gene from one parent. In erythrocytes from \u03b2-Thal+ subjects, the excess \u03b1-globin chains produce unstable \u03b1-tetramers, which can induce substantial oxidative stress leading to plasma membrane and cytoskeleton damage, as well as deranged cellular function. In the present study, we hypothesized that increased oxidative stress might lead to structural rearrangements in erythrocytes from \u03b2-Thal+ volunteers and functional alterations of ion transport proteins, including band 3 protein. The data obtained showed significant modifications of the cellular shape in erythrocytes from \u03b2-Thal+ subjects. In particular, a significantly increased number of elliptocytes was observed. Interestingly, iron overload, detected in erythrocytes from \u03b2-Thal+ subjects, provoked a significant production of reactive oxygen species (ROS), overactivation of the endogenous antioxidant enzymes catalase and superoxide dismutase, and glutathione depletion, resulting in (a) increased lipid peroxidation, (b) protein sulfhydryl group (-SH) oxidation. Iron overload-related oxidative stress affected Na+\/K+-ATPase activity, which in turn may have contributed to impaired \u03b2-Thal+ erythrocyte deformability. As a result, alterations in the distribution of cytoskeletal proteins, including \u03b1\/\u03b2-spectrin, protein 4.1, and \u03b1-actin, in erythrocytes from \u03b2-Thal+ subjects have been detected. Significantly, oxidative stress was also associated with increased phosphorylation and altered band 3 ion transport activity, as well as increased oxidized hemoglobin, which led to abnormal clustering and redistribution of band 3 on the plasma membrane. Taken together, these findings contribute to elucidating potential oxidative stress-related perturbations of ion transporters and associated cytoskeletal proteins, which may affect erythrocyte and systemic homeostasis in \u03b2-Thal+ subjects.<\/jats:p>","DOI":"10.3390\/ijms26041593","type":"journal-article","created":{"date-parts":[[2025,2,13]],"date-time":"2025-02-13T09:05:42Z","timestamp":1739437542000},"page":"1593","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Iron Overload-Related Oxidative Stress Leads to Hyperphosphorylation and Altered Anion Exchanger 1 (Band 3) Function in Erythrocytes from Subjects with \u03b2-Thalassemia Minor"],"prefix":"10.3390","volume":"26","author":[{"given":"Sara","family":"Spinelli","sequence":"first","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0784-9077","authenticated-orcid":false,"given":"Elisabetta","family":"Straface","sequence":"additional","affiliation":[{"name":"Biomarkers Unit, Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucrezia","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Biomarkers Unit, Center for Gender-Specific Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Caruso","sequence":"additional","affiliation":[{"name":"Complex Operational Unit of Clinical Pathology of Papardo Hospital, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6694-9249","authenticated-orcid":false,"given":"Silvia","family":"Dossena","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Research and Innovation Center Regenerative Medicine & Novel Therapies, Paracelsus Medical University, 5020 Salzburg, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6827-7327","authenticated-orcid":false,"given":"Angela","family":"Marino","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4904-4963","authenticated-orcid":false,"given":"Rossana","family":"Morabito","sequence":"additional","affiliation":[{"name":"Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9934-293X","authenticated-orcid":false,"given":"Alessia","family":"Remigante","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Dental and Morphological and Functional Imaging, University of Messina, 98166 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/S0140-6736(17)31822-6","article-title":"Thalassaemia","volume":"391","author":"Taher","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Storz, J.F. 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