{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T05:23:24Z","timestamp":1762925004597,"version":"3.45.0"},"reference-count":75,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The hitherto unknown thiol-disulfide redox potential (E0\u2032) of the \u03b293Cys residue in the HbS (\u03b26Glu\u2192Val) variant of human hemoglobin was calculated by MALDI-ToF mass spectrometry, which analyzes blood from a heterozygous carrier. To calculate the (E0\u2032) value, a redox equilibrium model was adopted, and the previously calculated value for wild-type \u03b2-Hb chain (E0\u2032 \u2212121 mV) was used. An E0\u2032 value of \u2212130.5 \u00b1 1.7 mV for the \u03b293Cys residue of HbS was obtained, thus a more reducing value than E0\u2032 in the wild-type isoform. Glutathionylation from this residue in the HbS tetramer lowers the extent of protein aggregation in fibrils and the clinical consequences, such as painful capillary occlusion and hemolysis. This finding confirmed the peculiar property of HbS as a more reactive scavenger of glutathione sulphinic acid (E0\u2032 = \u2212264 mV), which forms in the cytoplasm of red blood cells and reacts with structural and regulatory proteins, including hemoglobin. The ability to assess the erythrocyte oxidative status in sickle cell carriers can be developed into an additional functional test to rationally assess the effect of drug treatment and antioxidant dietary interventions on improving disease control.<\/jats:p>","DOI":"10.3390\/molecules30224342","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T13:51:08Z","timestamp":1762782668000},"page":"4342","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Redox Potential (E0\u2032) of the \u03b2-Chain 93Cys of HbS Measured with the Equilibrium Technique in a Heterozygous Sickle Cell Carrier Subject"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9620-1883","authenticated-orcid":false,"given":"Federico Maria","family":"Rubino","sequence":"first","affiliation":[{"name":"Department of Health Sciences, University of Milano, v. A. di Rudin\u00ec 8, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-9476-8208","authenticated-orcid":false,"given":"Aldijana","family":"Sadikovic","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Milano, v. A. di Rudin\u00ec 8, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0352-2819","authenticated-orcid":false,"given":"Camillo","family":"Morano","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Milano, v. A. di Rudin\u00ec 8, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7359-8558","authenticated-orcid":false,"given":"Michele","family":"Dei Cas","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Milano, v. A. di Rudin\u00ec 8, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2043-7846","authenticated-orcid":false,"given":"Monica","family":"Bignotto","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Milano, v. A. di Rudin\u00ec 8, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2988-0593","authenticated-orcid":false,"given":"Sara","family":"Ottolenghi","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, University of Milano Bicocca, 20126 Milan, Italy"},{"name":"Department of Emergency, Ospedale San Carlo Borromeo, ASST Santi Paolo e Carlo, 20172 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9672-3534","authenticated-orcid":false,"given":"Michele","family":"Mondoni","sequence":"additional","affiliation":[{"name":"Respiratory Unit, Department of Health Sciences, ASST Santi Paolo e Carlo, Universit\u00e0 degli Studi di Milano, 20145 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9260-3930","authenticated-orcid":false,"given":"Davide","family":"Chiumello","sequence":"additional","affiliation":[{"name":"Complex Structure of Anesthesia and Intensive Care, Department of Health Sciences, ASST Santi Paolo e Carlo, Universit\u00e0 degli Studi di Milano, 20145 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0705-340X","authenticated-orcid":false,"given":"Michele","family":"Samaja","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Milano, v. A. di Rudin\u00ec 8, 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-8860","authenticated-orcid":false,"given":"Rita","family":"Paroni","sequence":"additional","affiliation":[{"name":"Department of Health Sciences, University of Milano, v. 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