Protein Oxidation and Aging

TILMAN GRUNE, MD, is Full Professor and Director of the Institute of Nutrition at Friedrich Schiller University Jena. His research examines the biological phenomenon of oxidative stress. In particular, his research group has been investigating the oxidative stress response of cells and organisms and the protective influence of antioxidants.
 
BETUL CATALGOL, MD, is Assistant Professor in the Faculty of Medicine and the Department of Biochemistry at Marmara University. She is coauthor of Proteasome and Neurodegenerative Diseases, Proteasome and Cancer, and Protein Carbonyl Measurement by Enzyme-Linked Immunosorbent Assay.
 
TOBIAS JUNG, PhD, is a Research Assistant at Friedrich Schiller University Jena. He is coauthor of Structure of the Proteasome.

Reviews our current understanding of the role of protein oxidation in aging and age-related diseases
 
Protein oxidation is at the core of the aging process. Setting forth a variety of new methods and approaches, this book helps researchers conveniently by exploring the aging process and developing more effective therapies to prevent or treat age-related diseases. There have been many studies dedicated to the relationship between protein oxidation and age-related pathology; now it is possible for researchers and readers to learn new techniques as utilizing protein oxidation products as biomarkers for aging.
 
Protein Oxidation and Aging begins with a description of the tremendous variety of protein oxidation products. Furthermore, it covers:
* Major aspects of the protein oxidation process
* Cellular mechanisms for managing oxidized proteins
* Role of protein oxidation in aging
* Influence of genetic and environmental factors on protein oxidation
* Measuring protein oxidation in the aging process
* Protein oxidation in age-related diseases
 
References at the end of each chapter serve as a gateway to the growing body of original research studies and reviews in the field.

Introduction to the Wiley Series on Protein and Peptide Science xi
 
Preface xiii
 
1 Oxidative Stress and Protein Oxidation 1
 
1.1 The Large Variety of Protein Oxidation Products, 7
 
1.1.1 Primary Protein Oxidation Products, 7
 
1.1.1.1 Carbon-Centered Radicals, 9
 
1.1.1.2 Thiyl Radicals, 13
 
1.1.1.3 Aromatic Ring-Derived Radicals, 13
 
1.1.1.4 Transfer between Sites, 16
 
1.1.2 Reactive Compounds Mediating in Protein Oxidation, 18
 
1.1.2.1 Hydroxyl Radical, 20
 
1.1.2.2 Superoxide Radicals, 21
 
1.1.2.3 Hydrogen Peroxide, 24
 
1.1.2.4 Lipid Peroxyl Radicals, 24
 
1.1.2.5 Alkoxyl Radicals, 24
 
1.1.2.6 *NO and Peroxynitrite, 25
 
1.1.2.7 Hypochlorous Acid, 30
 
1.1.3 Enzymatic Systems Playing a Role in Protein Oxidation, 31
 
1.1.3.1 NADPH Oxidase, 32
 
1.1.3.2 Lipoxygenases, 35
 
1.1.3.3 Protein Kinases, 35
 
1.1.3.4 Mixed-Function Oxidases, 36
 
1.1.3.5 Nitric Oxide Synthetase (NOS), 38
 
1.1.3.6 Myeloperoxidase, 41
 
1.1.3.7 Cyclooxygenase, 42
 
1.1.4 Protein Oxidation in Cells and Cellular Structures, 43
 
1.1.4.1 Protein Oxidation in Blood and Blood Cells, 43
 
1.1.4.2 Protein Oxidation of Glycolytic Enzymes and Mitochondria, 46
 
1.1.4.2.1 Glycolytic Enzymes, 48
 
1.1.4.2.2 Aconitase, 49
 
1.1.4.2.3 Carnitine Palmitoyltransferase-1, 49
 
1.1.4.3 Cytochrome P450 Enzymes, 49
 
1.1.4.4 Protein Oxidation in the Nucleus and Chromatin, 50
 
1.1.4.4.1 Histone Modifi cation, 50
 
1.1.4.5 Protein Oxidation in the Endoplasmic Reticulum, 52
 
1.1.4.6 Protein Oxidation in Peroxisomes, 54
 
1.2 Reversible Oxidative Modifi cations, 55
 
1.2.1 Methionine Sulfoxides and Methionine Modifi cations, 55
 
1.2.2 Cysteine Modifi cations and Disulfi de Bond Formation, 61
 
1.2.3 Surface Hydrophobicity Modifi cations, 64
 
1.3 Irreversible Oxidation Products, 64
 
1.3.1 Protein Oxidation and Enzymatic Posttranslational Modifications, 65
 
1.3.2 Deamidation and Transamination, 66
 
1.3.3 Protein Glycation and AGEs, 67
 
1.3.3.1 Receptor for Advanced Glycation End Products (RAGE), 75
 
1.3.3.2 Nepsilon-Carboxymethyllysine and Nepsilon-Carboxyethyllysine, 76
 
1.3.3.3 Pentosidine, 76
 
1.3.4 Racemization, 77
 
1.3.5 Nitrosylation, 77
 
1.3.6 Tyrosyl Radicals and Nitrotyrosines, 78
 
1.3.6.1 Dityrosines, 79
 
1.3.7 Protein Carbonyls, 80
 
1.3.8 Aldehyde-Protein Reactions, 81
 
1.3.8.1 MDA-Protein Adducts, 82
 
1.3.8.2 4-Hydroxy-2,3-Nonenal-Protein Adducts, 82
 
1.3.9 Cross-Linking of Proteins, 82
 
1.4 The Oxidation of Extracellular Matrix, Membrane and Cytoskeletal Proteins, 83
 
1.4.1 Collagen, 84
 
1.4.2 Elastin, 95
 
1.4.3 The Oxidation of Membrane Proteins, 97
 
1.4.4 Band 3, 97
 
1.4.5 Actin, 99
 
1.5 Mechanism and Factors Influencing the Formation of Protein Oxidation Products, 100
 
1.5.1 Redox Status, 101
 
1.5.2 Protein Turnover, 106
 
1.5.3 Metal-Catalyzed Oxidation (MCO), 107
 
1.5.4 Heat Shock Proteins, 109
 
1.6 Protein Aggregates: Formation and Specific Metabolic Effects, 111
 
1.6.1 Accumulation of Oxidized Proteins, 113
 
1.6.2 Lipofuscin and Ceroid, 115
 
1.7 Methods to Measure Protein Oxidation Products in Research Laboratories, 119
 
1.7.1 Determination of Methionine Sulfoxide Reduction and Methionine Oxidation, 120
 
1.7.2 Determination of Prote