Sánchez-Jaut, SandraPérez-Benavente, SusanaAbad, PalomaMéndez Cuadro, DaríoPuyet Catalina, AntonioDíez Martín, AmaliaGalicia Poblet, GonzaloGómez Domínguez, ElenaMoran Jiménez, María J.Bautista Santa Cruz, José ManuelAzcárate, Isabel G.2024-01-192024-01-192023-02-02Sánchez-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/ijms240329221422-006710.3390/ijms24032922https://hdl.handle.net/20.500.14352/94131Iron 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.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://www.mdpi.com/1422-0067/24/3/2922open access6HemochromatosisOxidative stress4-Hydroxynonenal (HNE)Erythrocyte membrane proteinsProtein modificationCiencias Biomédicas24 Ciencias de la Vida