Protein Susceptibility to Peroxidation by 4-Hydroxynonenal in Hereditary Hemochromatosis.
Sandra Sánchez-JautSusana Pérez-BenaventePaloma AbadDarío Méndez CuadroAntonio PuyetAmalia DiezGonzalo Galicia-PobletElena Gómez-DomínguezMaría J Moran-JiménezJosé M BautistaIsabel G AzcáratePublished in: International journal of molecular sciences (2023)
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.
Keyphrases
- end stage renal disease
- mass spectrometry
- oxidative stress
- ejection fraction
- newly diagnosed
- mouse model
- chronic kidney disease
- reactive oxygen species
- endothelial cells
- ms ms
- protein protein
- type diabetes
- peritoneal dialysis
- binding protein
- high fat diet induced
- amino acid
- dna damage
- metabolic syndrome
- multiple sclerosis
- adipose tissue
- white matter
- nitric oxide
- brain injury
- heat shock protein
- cerebral ischemia
- subarachnoid hemorrhage
- heat stress
- wound healing
- induced pluripotent stem cells