RT Journal Article T1 Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis A1 Sánchez-Jaut, Sandra A1 Pérez-Benavente, Susana A1 Abad, Paloma A1 Méndez Cuadro, Darío A1 Puyet Catalina, Antonio A1 Díez Martín, Amalia A1 Galicia Poblet, Gonzalo A1 Gómez Domínguez, Elena A1 Moran Jiménez, María J. A1 Bautista Santa Cruz, José Manuel A1 Azcárate, Isabel G. AB Iron overload caused by hereditary hemochromatosis (HH) increases free reactive oxygen species that, in turn, induce lipid peroxidation. Its 4-hydroxynonenal (HNE) by-product is a wellestablished marker of lipid peroxidation since it reacts with accessible proteins with deleterious consequences. Indeed, elevated levels of HNE are often detected in a wide variety of human diseases related to oxidative stress. Here, we evaluated HNE-modified proteins in the membrane of erythrocytes from HH patients and in organs of Hfe−/− male and female mice, a mouse model of HH. For this purpose, we used one- and two-dimensional gel electrophoresis, immunoblotting and MALDI-TOF/TOF analysis. We identified cytoskeletal membrane proteins and membrane receptors of erythrocytes bound to HNE exclusively in HH patients. Furthermore, kidney and brain of Hfe−/−mice contained more HNE-adducted protein than healthy controls. Our results identified main HNE-modified proteins suggesting that HH favours preferred protein targets for oxidation by HNE. SN 1422-0067 YR 2023 FD 2023-02-02 LK https://hdl.handle.net/20.500.14352/94131 UL https://hdl.handle.net/20.500.14352/94131 LA eng NO Sánchez-Jaut, S.; Pérez-Benavente, S.; Abad, P.; Méndez-Cuadro, D.; Puyet, A.; Diez, A.; Galicia-Poblet, G.; Gómez-Domínguez, E.; Moran-Jiménez, M.J.; Bautista, J.M.; et al. Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis. Int. J. Mol. Sci. 2023, 24, 2922. https:// doi.org/10.3390/ijms24032922 NO Ramón Areces Foundation. DS Docta Complutense RD 7 abr 2025