Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis

• Published in: International journal of molecular sciences 2023-02, Vol.24 (3), p.2922
• Main Authors: Sánchez-Jaut, Sandra, Pérez-Benavente, Susana, Abad, Paloma, Méndez-Cuadro, Darío, Puyet, Antonio, Diez, Amalia, Galicia-Poblet, Gonzalo, Gómez-Domínguez, Elena, Moran-Jiménez, María J, Bautista, José M, Azcárate, Isabel G
• Format: Article
• Language: English
• Subjects: 4-Hydroxynonenal; 4-hydroxynonenal (HNE); Aldehydes - metabolism; Animals; Apoptosis; Cardiovascular disease; Cell cycle; Cell division; Cytoskeleton; Diabetes; Electrophoresis; erythrocyte membrane proteins; Erythrocytes; Female; Females; Gel electrophoresis; Glycoproteins; Heart; Hemochromatosis; Hemochromatosis - genetics; Hemochromatosis Protein - genetics; Hemochromatosis Protein - metabolism; Hemoglobin; Hfe−/− mouse; Homeostasis; Humans; Immunoblotting; Iron; Iron Overload; Lipid Peroxidation; Lipids; Liver; Male; Males; Membrane proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; Membranes; Mice; Mutation; Oxidation; Oxidative stress; Parkinson's disease; Patients; Peptides; Proteins; Reactive oxygen species; Toxicity
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24032922

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 well-established 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.