4-Hydroxynonenal (HNE) modified proteins in metabolic diseases.
4-Hydroxynonenal (HNE) is one of the quantitatively most important products of lipid peroxidation. Due to its high toxicity it is quickly metabolized, however, a small share of HNE avoids enzymatic detoxification and reacts with biomolecules including proteins. The formation of HNE-protein-adducts is one of the accompanying processes in oxidative stress or redox disbalance. The modification of proteins might occur at several amino acids side chains, leading to a variety of products and having effects on the protein function and fate. This review summarizes current knowledge on the formation of HNE-modified proteins, their fate in mammalian cells and their potential role as a damaging agents during oxidative stress. Furthermore, the potential of HNE-modified proteins as biomarkers for several diseases are highlighted.
Department of Molecular Toxicology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany; German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany; Department of Biomedicine, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal; Institute for Innovation and Health Research (I3S), Aging and Stress Group, R. Alfredo Allen, 4200-135 Porto, Portugal.
José Pedro
JP
Castro
Department of Molecular Toxicology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany; German Center for Cardiovascular Research (DZHK), 10117 Berlin, Germany.
Tobias
T
Jung
Department of Molecular Toxicology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Germany; German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany; German Center for Cardiovascular Research (DZHK), 10117 Berlin, Germany; NutriAct - Competence Cluster for Nutritional Sciences Berlin-Potsdam, Germany. Electronic address: tilman.grune@dife.de.
Tilman
T
Grune
Institute of Physiotherapy and Gerontology of Kortexmed, 38667 Bad Harzburg, Germany; University of Salzburg, Institute of Biology, Department of Cellular Physiology, A-5020 Salzburg, Austria.
Werner
W
Siems
D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism; D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D015227:Lipid Peroxidation; D008659:Metabolic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D059748:Proteolysis
D000447:Aldehydes; D015415:Biomarkers; D006360:Heat-Shock Proteins; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D005982:Glutathione Transferase; D046988:Proteasome Endopeptidase Complex; C027576:4-hydroxy-2-nonenal
4-hydroxynonenal; HNE metabolism; HNE-modified Proteins; Proteasome; Proteolysis