Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis

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. In...

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Main Authors: Sandra Sánchez-Jaut, Susana Pérez-Benavente, Paloma Abad, Darío Méndez-Cuadro, Antonio Puyet, Amalia Diez, Gonzalo Galicia-Poblet, Elena Gómez-Domínguez, María J. Moran-Jiménez, José M. Bautista, Isabel G. Azcárate
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/3/2922
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author Sandra Sánchez-Jaut
Susana Pérez-Benavente
Paloma Abad
Darío Méndez-Cuadro
Antonio Puyet
Amalia Diez
Gonzalo Galicia-Poblet
Elena Gómez-Domínguez
María J. Moran-Jiménez
José M. Bautista
Isabel G. Azcárate
author_facet Sandra Sánchez-Jaut
Susana Pérez-Benavente
Paloma Abad
Darío Méndez-Cuadro
Antonio Puyet
Amalia Diez
Gonzalo Galicia-Poblet
Elena Gómez-Domínguez
María J. Moran-Jiménez
José M. Bautista
Isabel G. Azcárate
author_sort Sandra Sánchez-Jaut
collection DOAJ
description 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<sup>−/−</sup> 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<sup>−/−</sup> 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.
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spelling doaj.art-2b79ecf09184442ea410407afce789352023-11-16T17:04:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01243292210.3390/ijms24032922Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary HemochromatosisSandra Sánchez-Jaut0Susana Pérez-Benavente1Paloma Abad2Darío Méndez-Cuadro3Antonio Puyet4Amalia Diez5Gonzalo Galicia-Poblet6Elena Gómez-Domínguez7María J. Moran-Jiménez8José M. Bautista9Isabel G. Azcárate10Department of Biochemistry and Molecular Biology, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, Complutense University of Madrid, 28040 Madrid, SpainAnalytical Chemistry and Biomedicine Group, School of Exact and Natural Sciences, San Pablo Campus, University of Cartagena, Cartagena 130014, ColombiaDepartment of Biochemistry and Molecular Biology, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Biochemistry and Molecular Biology, Complutense University of Madrid, 28040 Madrid, SpainPediatric Digestive Service, Guadalajara University Hospital, 19002 Guadalajara, SpainResearch Institute Hospital 12 de Octubre, 28041 Madrid, SpainResearch Institute Hospital 12 de Octubre, 28041 Madrid, SpainDepartment of Biochemistry and Molecular Biology, Complutense University of Madrid, 28040 Madrid, SpainDepartment of Medical Specialties and Public Health, Rey Juan Carlos University, 28922 Madrid, SpainIron 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<sup>−/−</sup> 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<sup>−/−</sup> 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.https://www.mdpi.com/1422-0067/24/3/2922hemochromatosisoxidative stresslipid peroxidation4-hydroxynonenal (HNE)Hfe<sup>−/−</sup> mouseerythrocyte membrane proteins
spellingShingle Sandra Sánchez-Jaut
Susana Pérez-Benavente
Paloma Abad
Darío Méndez-Cuadro
Antonio Puyet
Amalia Diez
Gonzalo Galicia-Poblet
Elena Gómez-Domínguez
María J. Moran-Jiménez
José M. Bautista
Isabel G. Azcárate
Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis
International Journal of Molecular Sciences
hemochromatosis
oxidative stress
lipid peroxidation
4-hydroxynonenal (HNE)
Hfe<sup>−/−</sup> mouse
erythrocyte membrane proteins
title Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis
title_full Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis
title_fullStr Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis
title_full_unstemmed Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis
title_short Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis
title_sort protein susceptibility to peroxidation by 4 hydroxynonenal in hereditary hemochromatosis
topic hemochromatosis
oxidative stress
lipid peroxidation
4-hydroxynonenal (HNE)
Hfe<sup>−/−</sup> mouse
erythrocyte membrane proteins
url https://www.mdpi.com/1422-0067/24/3/2922
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