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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…mehr
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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.
Produktdetails
- Produktdetails
- Verlag: John Wiley & Sons
- Seitenzahl: 516
- Erscheinungstermin: 7. November 2012
- Englisch
- ISBN-13: 9781118492994
- Artikelnr.: 37353899
- Verlag: John Wiley & Sons
- Seitenzahl: 516
- Erscheinungstermin: 7. November 2012
- Englisch
- ISBN-13: 9781118492994
- Artikelnr.: 37353899
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.
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 Protein Glycation and Adducts
121 1.7.3 Analysis of Isoaspartate Formation
122 1.7.4 Measurement of Fragmentation
122 1.7.5 Measurement of Tyrosine Oxidation
123 1.7.6 Protein Carbonyl Measurement
124 1.7.7 Radioactive Labeling Protocols for Proteolysis and Aggregation Measurements
128 1.7.8 Standard Chromatographic Methods for the Measurement of Protein Modifi cations
132 1.7.9 Liquid Chromatography Techniques Supported by Mass Spectrometry
133 1.7.10 GC/MS
134 1.7.11 Analysis of Protein-Bound 3-Nitrotyrosine by a Competitive ELISA Method
134 1.7.12 Protein Oxidation Products as Biomarkers in Clinical Science
135 References
139 2 Removal of Oxidized Proteins 215 2.1 The Limited Repair of Some Oxidized Proteins
216 2.1.1 Thiol Repair
216 2.1.2 Methionine Sulfoxide Reductases
219 2.2 Proteolysis
221 2.2.1 The Proteasomal System and Its Role in the Degradation of Oxidized Proteins
222 2.2.1.1 The Ubiquitin-Proteasome System (UPS)
222 2.2.1.2 The Components of the UPS
222 2.2.1.2.1 The 20S Proteasome
222 2.2.1.2.2 The Inducible Forms of the Proteasome and Their Function
227 2.2.1.2.3 The 11S Regulator
231 2.2.1.2.4 The 19S Regulator and the UPS
233 2.2.1.2.5 The PA200 Regulator Protein
238 2.2.1.2.6 Cellular Proteasome Inhibitors
239 2.2.1.3 Low-Molecular-Weight Proteasome Inhibitors
239 2.2.1.4 Cellular Function of the UPS
241 2.2.1.5 The Degradation of Oxidized Proteins: A Function of the 20S Proteasome
243 2.2.1.5.1 Early Studies on the Turnover of Oxidized Proteins
244 2.2.1.5.2 In Vitro Studies and the Recognition of Oxidized Proteins by the Proteasome
244 2.2.1.5.3 Cellular and In Vivo Studies of the Degradation of Oxidized Proteins
248 2.2.1.5.4 The Inhibition of the Proteasome by Cross-Linked Oxidized Proteins and Proteasomal Regulation during Oxidative Stress
251 2.3 The Role of Other Proteases in the Fate of Oxidized Proteins
254 2.3.1 Lysosomal Degradation of Oxidized Proteins and the Role of Autophagy
254 2.3.2 Mitochondrial Degradation of Oxidized Proteins and the Lon Protease
256 2.3.3 The Uptake of Extracellular Oxidized Proteins and the Role of the Proteasome in Their Degradation
258 2.3.4 Calpains and the Degradation of Oxidized Proteins
259 2.4 Role of Heat Shock Proteins in Protein Degradation
260 2.5 Conclusion
262 References
262 3 Protein Oxidation and Aging: Different Model Systems and Affecting Factors 295 3.1 Protein Oxidation during Aging: Lower Organisms and Cellular Model Systems
297 3.1.1 Yeast
297 3.1.1.1 Saccharomyces cerevisiae
297 3.1.1.2 Schizosaccharomyces pombe
301 3.1.2 Podospora anserina
301 3.1.3 Bacteria
302 3.1.3.1 Escherichia coli
302 3.1.4 Cell Cultures
304 3.2 Nonmammalian Model Systems and the Accumulation of Oxidized Proteins during Aging
308 3.2.1 Caenorhabditis elegans
308 3.2.2 Drosophila melanogaster
310 3.2.3 Aquatic Systems
313 3.2.4 Plants
315 3.2.5 Amphibians
317 3.3 Age-Related Protein Oxidation in Humans and Mammals
317 3.3.1 Humans
317 3.3.2 Animals
319 3.3.2.1 Rabbits
323 3.3.2.2 Mice
324 3.3.2.3 Rats
327 3.3.2.4 Gerbils
329 3.3.2.5 Primates
330 3.4 Inherited Factors Influencing Protein Oxidation during Aging
331 3.4.1 Genetic Instability
Mutations
and Polymorphism
331 3.4.2 Gender
333 3.4.3 Vitagenes
334 3.4.4 Signal Transduction and Transcription Factors
335 3.4.5 Ion Channels
340 3.5 Age-Related Protein Aggregate Formation in Model Systems
341 3.6 Environmental Factors Affecting Healthy Aging
342 3.6.1 UV-Induced Skin Photoaging and Skin Aging
344 3.6.2 Pesticides
348 3.6.3 Exercise
349 3.6.4 Dietary Factors and Prevention Strategies
351 3.6.4.1 Melatonin
353 3.6.4.2 Growth Hormone
354 3.6.4.3 Biotrace Metal Elements: Zinc
356 3.6.4.4 Ascorbic Acid
357 3.6.4.5 Vitamin E
360 3.6.4.6 Carnitine and Acetyl-L-Carnitine
361 3.6.4.7 Homocysteine
362 3.6.4.8 Ubiquinone
Coenzyme Q10
363 3.6.4.9 Carnosine
363 3.6.4.10 Lipoic Acid
364 3.6.4.11 N-Acetyl-L-Cysteine
365 3.6.5 Pharmacological Response and Biotransformation in Aging
365 3.6.5.1 Plant Extracts
366 3.6.5.2 Polyphenols and Flavonoids
366 3.6.5.3 Resveratrol
367 3.6.5.4 AGE and ALE Inhibitors
368 3.6.6 Caloric Restriction
369 3.7 Repair and Degradation of Oxidized Proteins during Aging
370 References
372 4 Protein Oxidation in Some Age-Related Diseases 417 4.1 Protein Oxidation during Neurodegeneration and Neurological Diseases
417 4.1.1 Brain Aging
418 4.1.2 Alzheimer's Disease
420 4.1.3 Parkinson's Disease
424 4.1.4 Huntington's Disease
425 4.1.5 Stroke
427 4.1.6 Amyotrophic Lateral Sclerosis
427 4.2 Protein Oxidation in Cardiac Diseases
429 4.2.1 Ischemia-Reperfusion
429 4.2.2 Atherosclerosis
430 4.3 Protein Oxidation in Diabetes
431 4.4 Protein Oxidation in Degenerative Arthritis
434 4.5 Protein Oxidation in Muscle Wasting and Sarcopenia
435 4.6 Protein Oxidation in Destructive Eye Diseases
437 4.6.1 Age-Related Macular Degeneration
437 4.6.2 Cataract
438 4.7 Protein Oxidation in Osteoporosis
440 4.8 Protein Oxidation in Cancer
441 4.8.1 Proteasome Inhibitors in Cancer Therapy
444 4.9 Other Diseases
446 4.9.1 Premature Aging Diseases Progeria and Werner's Syndrome
446 4.9.2 Renal Failure and Hemodialysis in Elderly People
447 4.9.3 Obesity
447 4.9.4 Idiopathic Pulmonary Fibrosis
448 4.9.5 Presbycusis (Age-Related Hear Loss)
448 References
448 List of Abbreviations 479 Index 493
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 Protein Glycation and Adducts
121 1.7.3 Analysis of Isoaspartate Formation
122 1.7.4 Measurement of Fragmentation
122 1.7.5 Measurement of Tyrosine Oxidation
123 1.7.6 Protein Carbonyl Measurement
124 1.7.7 Radioactive Labeling Protocols for Proteolysis and Aggregation Measurements
128 1.7.8 Standard Chromatographic Methods for the Measurement of Protein Modifi cations
132 1.7.9 Liquid Chromatography Techniques Supported by Mass Spectrometry
133 1.7.10 GC/MS
134 1.7.11 Analysis of Protein-Bound 3-Nitrotyrosine by a Competitive ELISA Method
134 1.7.12 Protein Oxidation Products as Biomarkers in Clinical Science
135 References
139 2 Removal of Oxidized Proteins 215 2.1 The Limited Repair of Some Oxidized Proteins
216 2.1.1 Thiol Repair
216 2.1.2 Methionine Sulfoxide Reductases
219 2.2 Proteolysis
221 2.2.1 The Proteasomal System and Its Role in the Degradation of Oxidized Proteins
222 2.2.1.1 The Ubiquitin-Proteasome System (UPS)
222 2.2.1.2 The Components of the UPS
222 2.2.1.2.1 The 20S Proteasome
222 2.2.1.2.2 The Inducible Forms of the Proteasome and Their Function
227 2.2.1.2.3 The 11S Regulator
231 2.2.1.2.4 The 19S Regulator and the UPS
233 2.2.1.2.5 The PA200 Regulator Protein
238 2.2.1.2.6 Cellular Proteasome Inhibitors
239 2.2.1.3 Low-Molecular-Weight Proteasome Inhibitors
239 2.2.1.4 Cellular Function of the UPS
241 2.2.1.5 The Degradation of Oxidized Proteins: A Function of the 20S Proteasome
243 2.2.1.5.1 Early Studies on the Turnover of Oxidized Proteins
244 2.2.1.5.2 In Vitro Studies and the Recognition of Oxidized Proteins by the Proteasome
244 2.2.1.5.3 Cellular and In Vivo Studies of the Degradation of Oxidized Proteins
248 2.2.1.5.4 The Inhibition of the Proteasome by Cross-Linked Oxidized Proteins and Proteasomal Regulation during Oxidative Stress
251 2.3 The Role of Other Proteases in the Fate of Oxidized Proteins
254 2.3.1 Lysosomal Degradation of Oxidized Proteins and the Role of Autophagy
254 2.3.2 Mitochondrial Degradation of Oxidized Proteins and the Lon Protease
256 2.3.3 The Uptake of Extracellular Oxidized Proteins and the Role of the Proteasome in Their Degradation
258 2.3.4 Calpains and the Degradation of Oxidized Proteins
259 2.4 Role of Heat Shock Proteins in Protein Degradation
260 2.5 Conclusion
262 References
262 3 Protein Oxidation and Aging: Different Model Systems and Affecting Factors 295 3.1 Protein Oxidation during Aging: Lower Organisms and Cellular Model Systems
297 3.1.1 Yeast
297 3.1.1.1 Saccharomyces cerevisiae
297 3.1.1.2 Schizosaccharomyces pombe
301 3.1.2 Podospora anserina
301 3.1.3 Bacteria
302 3.1.3.1 Escherichia coli
302 3.1.4 Cell Cultures
304 3.2 Nonmammalian Model Systems and the Accumulation of Oxidized Proteins during Aging
308 3.2.1 Caenorhabditis elegans
308 3.2.2 Drosophila melanogaster
310 3.2.3 Aquatic Systems
313 3.2.4 Plants
315 3.2.5 Amphibians
317 3.3 Age-Related Protein Oxidation in Humans and Mammals
317 3.3.1 Humans
317 3.3.2 Animals
319 3.3.2.1 Rabbits
323 3.3.2.2 Mice
324 3.3.2.3 Rats
327 3.3.2.4 Gerbils
329 3.3.2.5 Primates
330 3.4 Inherited Factors Influencing Protein Oxidation during Aging
331 3.4.1 Genetic Instability
Mutations
and Polymorphism
331 3.4.2 Gender
333 3.4.3 Vitagenes
334 3.4.4 Signal Transduction and Transcription Factors
335 3.4.5 Ion Channels
340 3.5 Age-Related Protein Aggregate Formation in Model Systems
341 3.6 Environmental Factors Affecting Healthy Aging
342 3.6.1 UV-Induced Skin Photoaging and Skin Aging
344 3.6.2 Pesticides
348 3.6.3 Exercise
349 3.6.4 Dietary Factors and Prevention Strategies
351 3.6.4.1 Melatonin
353 3.6.4.2 Growth Hormone
354 3.6.4.3 Biotrace Metal Elements: Zinc
356 3.6.4.4 Ascorbic Acid
357 3.6.4.5 Vitamin E
360 3.6.4.6 Carnitine and Acetyl-L-Carnitine
361 3.6.4.7 Homocysteine
362 3.6.4.8 Ubiquinone
Coenzyme Q10
363 3.6.4.9 Carnosine
363 3.6.4.10 Lipoic Acid
364 3.6.4.11 N-Acetyl-L-Cysteine
365 3.6.5 Pharmacological Response and Biotransformation in Aging
365 3.6.5.1 Plant Extracts
366 3.6.5.2 Polyphenols and Flavonoids
366 3.6.5.3 Resveratrol
367 3.6.5.4 AGE and ALE Inhibitors
368 3.6.6 Caloric Restriction
369 3.7 Repair and Degradation of Oxidized Proteins during Aging
370 References
372 4 Protein Oxidation in Some Age-Related Diseases 417 4.1 Protein Oxidation during Neurodegeneration and Neurological Diseases
417 4.1.1 Brain Aging
418 4.1.2 Alzheimer's Disease
420 4.1.3 Parkinson's Disease
424 4.1.4 Huntington's Disease
425 4.1.5 Stroke
427 4.1.6 Amyotrophic Lateral Sclerosis
427 4.2 Protein Oxidation in Cardiac Diseases
429 4.2.1 Ischemia-Reperfusion
429 4.2.2 Atherosclerosis
430 4.3 Protein Oxidation in Diabetes
431 4.4 Protein Oxidation in Degenerative Arthritis
434 4.5 Protein Oxidation in Muscle Wasting and Sarcopenia
435 4.6 Protein Oxidation in Destructive Eye Diseases
437 4.6.1 Age-Related Macular Degeneration
437 4.6.2 Cataract
438 4.7 Protein Oxidation in Osteoporosis
440 4.8 Protein Oxidation in Cancer
441 4.8.1 Proteasome Inhibitors in Cancer Therapy
444 4.9 Other Diseases
446 4.9.1 Premature Aging Diseases Progeria and Werner's Syndrome
446 4.9.2 Renal Failure and Hemodialysis in Elderly People
447 4.9.3 Obesity
447 4.9.4 Idiopathic Pulmonary Fibrosis
448 4.9.5 Presbycusis (Age-Related Hear Loss)
448 References
448 List of Abbreviations 479 Index 493
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 Protein Glycation and Adducts
121 1.7.3 Analysis of Isoaspartate Formation
122 1.7.4 Measurement of Fragmentation
122 1.7.5 Measurement of Tyrosine Oxidation
123 1.7.6 Protein Carbonyl Measurement
124 1.7.7 Radioactive Labeling Protocols for Proteolysis and Aggregation Measurements
128 1.7.8 Standard Chromatographic Methods for the Measurement of Protein Modifi cations
132 1.7.9 Liquid Chromatography Techniques Supported by Mass Spectrometry
133 1.7.10 GC/MS
134 1.7.11 Analysis of Protein-Bound 3-Nitrotyrosine by a Competitive ELISA Method
134 1.7.12 Protein Oxidation Products as Biomarkers in Clinical Science
135 References
139 2 Removal of Oxidized Proteins 215 2.1 The Limited Repair of Some Oxidized Proteins
216 2.1.1 Thiol Repair
216 2.1.2 Methionine Sulfoxide Reductases
219 2.2 Proteolysis
221 2.2.1 The Proteasomal System and Its Role in the Degradation of Oxidized Proteins
222 2.2.1.1 The Ubiquitin-Proteasome System (UPS)
222 2.2.1.2 The Components of the UPS
222 2.2.1.2.1 The 20S Proteasome
222 2.2.1.2.2 The Inducible Forms of the Proteasome and Their Function
227 2.2.1.2.3 The 11S Regulator
231 2.2.1.2.4 The 19S Regulator and the UPS
233 2.2.1.2.5 The PA200 Regulator Protein
238 2.2.1.2.6 Cellular Proteasome Inhibitors
239 2.2.1.3 Low-Molecular-Weight Proteasome Inhibitors
239 2.2.1.4 Cellular Function of the UPS
241 2.2.1.5 The Degradation of Oxidized Proteins: A Function of the 20S Proteasome
243 2.2.1.5.1 Early Studies on the Turnover of Oxidized Proteins
244 2.2.1.5.2 In Vitro Studies and the Recognition of Oxidized Proteins by the Proteasome
244 2.2.1.5.3 Cellular and In Vivo Studies of the Degradation of Oxidized Proteins
248 2.2.1.5.4 The Inhibition of the Proteasome by Cross-Linked Oxidized Proteins and Proteasomal Regulation during Oxidative Stress
251 2.3 The Role of Other Proteases in the Fate of Oxidized Proteins
254 2.3.1 Lysosomal Degradation of Oxidized Proteins and the Role of Autophagy
254 2.3.2 Mitochondrial Degradation of Oxidized Proteins and the Lon Protease
256 2.3.3 The Uptake of Extracellular Oxidized Proteins and the Role of the Proteasome in Their Degradation
258 2.3.4 Calpains and the Degradation of Oxidized Proteins
259 2.4 Role of Heat Shock Proteins in Protein Degradation
260 2.5 Conclusion
262 References
262 3 Protein Oxidation and Aging: Different Model Systems and Affecting Factors 295 3.1 Protein Oxidation during Aging: Lower Organisms and Cellular Model Systems
297 3.1.1 Yeast
297 3.1.1.1 Saccharomyces cerevisiae
297 3.1.1.2 Schizosaccharomyces pombe
301 3.1.2 Podospora anserina
301 3.1.3 Bacteria
302 3.1.3.1 Escherichia coli
302 3.1.4 Cell Cultures
304 3.2 Nonmammalian Model Systems and the Accumulation of Oxidized Proteins during Aging
308 3.2.1 Caenorhabditis elegans
308 3.2.2 Drosophila melanogaster
310 3.2.3 Aquatic Systems
313 3.2.4 Plants
315 3.2.5 Amphibians
317 3.3 Age-Related Protein Oxidation in Humans and Mammals
317 3.3.1 Humans
317 3.3.2 Animals
319 3.3.2.1 Rabbits
323 3.3.2.2 Mice
324 3.3.2.3 Rats
327 3.3.2.4 Gerbils
329 3.3.2.5 Primates
330 3.4 Inherited Factors Influencing Protein Oxidation during Aging
331 3.4.1 Genetic Instability
Mutations
and Polymorphism
331 3.4.2 Gender
333 3.4.3 Vitagenes
334 3.4.4 Signal Transduction and Transcription Factors
335 3.4.5 Ion Channels
340 3.5 Age-Related Protein Aggregate Formation in Model Systems
341 3.6 Environmental Factors Affecting Healthy Aging
342 3.6.1 UV-Induced Skin Photoaging and Skin Aging
344 3.6.2 Pesticides
348 3.6.3 Exercise
349 3.6.4 Dietary Factors and Prevention Strategies
351 3.6.4.1 Melatonin
353 3.6.4.2 Growth Hormone
354 3.6.4.3 Biotrace Metal Elements: Zinc
356 3.6.4.4 Ascorbic Acid
357 3.6.4.5 Vitamin E
360 3.6.4.6 Carnitine and Acetyl-L-Carnitine
361 3.6.4.7 Homocysteine
362 3.6.4.8 Ubiquinone
Coenzyme Q10
363 3.6.4.9 Carnosine
363 3.6.4.10 Lipoic Acid
364 3.6.4.11 N-Acetyl-L-Cysteine
365 3.6.5 Pharmacological Response and Biotransformation in Aging
365 3.6.5.1 Plant Extracts
366 3.6.5.2 Polyphenols and Flavonoids
366 3.6.5.3 Resveratrol
367 3.6.5.4 AGE and ALE Inhibitors
368 3.6.6 Caloric Restriction
369 3.7 Repair and Degradation of Oxidized Proteins during Aging
370 References
372 4 Protein Oxidation in Some Age-Related Diseases 417 4.1 Protein Oxidation during Neurodegeneration and Neurological Diseases
417 4.1.1 Brain Aging
418 4.1.2 Alzheimer's Disease
420 4.1.3 Parkinson's Disease
424 4.1.4 Huntington's Disease
425 4.1.5 Stroke
427 4.1.6 Amyotrophic Lateral Sclerosis
427 4.2 Protein Oxidation in Cardiac Diseases
429 4.2.1 Ischemia-Reperfusion
429 4.2.2 Atherosclerosis
430 4.3 Protein Oxidation in Diabetes
431 4.4 Protein Oxidation in Degenerative Arthritis
434 4.5 Protein Oxidation in Muscle Wasting and Sarcopenia
435 4.6 Protein Oxidation in Destructive Eye Diseases
437 4.6.1 Age-Related Macular Degeneration
437 4.6.2 Cataract
438 4.7 Protein Oxidation in Osteoporosis
440 4.8 Protein Oxidation in Cancer
441 4.8.1 Proteasome Inhibitors in Cancer Therapy
444 4.9 Other Diseases
446 4.9.1 Premature Aging Diseases Progeria and Werner's Syndrome
446 4.9.2 Renal Failure and Hemodialysis in Elderly People
447 4.9.3 Obesity
447 4.9.4 Idiopathic Pulmonary Fibrosis
448 4.9.5 Presbycusis (Age-Related Hear Loss)
448 References
448 List of Abbreviations 479 Index 493
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 Protein Glycation and Adducts
121 1.7.3 Analysis of Isoaspartate Formation
122 1.7.4 Measurement of Fragmentation
122 1.7.5 Measurement of Tyrosine Oxidation
123 1.7.6 Protein Carbonyl Measurement
124 1.7.7 Radioactive Labeling Protocols for Proteolysis and Aggregation Measurements
128 1.7.8 Standard Chromatographic Methods for the Measurement of Protein Modifi cations
132 1.7.9 Liquid Chromatography Techniques Supported by Mass Spectrometry
133 1.7.10 GC/MS
134 1.7.11 Analysis of Protein-Bound 3-Nitrotyrosine by a Competitive ELISA Method
134 1.7.12 Protein Oxidation Products as Biomarkers in Clinical Science
135 References
139 2 Removal of Oxidized Proteins 215 2.1 The Limited Repair of Some Oxidized Proteins
216 2.1.1 Thiol Repair
216 2.1.2 Methionine Sulfoxide Reductases
219 2.2 Proteolysis
221 2.2.1 The Proteasomal System and Its Role in the Degradation of Oxidized Proteins
222 2.2.1.1 The Ubiquitin-Proteasome System (UPS)
222 2.2.1.2 The Components of the UPS
222 2.2.1.2.1 The 20S Proteasome
222 2.2.1.2.2 The Inducible Forms of the Proteasome and Their Function
227 2.2.1.2.3 The 11S Regulator
231 2.2.1.2.4 The 19S Regulator and the UPS
233 2.2.1.2.5 The PA200 Regulator Protein
238 2.2.1.2.6 Cellular Proteasome Inhibitors
239 2.2.1.3 Low-Molecular-Weight Proteasome Inhibitors
239 2.2.1.4 Cellular Function of the UPS
241 2.2.1.5 The Degradation of Oxidized Proteins: A Function of the 20S Proteasome
243 2.2.1.5.1 Early Studies on the Turnover of Oxidized Proteins
244 2.2.1.5.2 In Vitro Studies and the Recognition of Oxidized Proteins by the Proteasome
244 2.2.1.5.3 Cellular and In Vivo Studies of the Degradation of Oxidized Proteins
248 2.2.1.5.4 The Inhibition of the Proteasome by Cross-Linked Oxidized Proteins and Proteasomal Regulation during Oxidative Stress
251 2.3 The Role of Other Proteases in the Fate of Oxidized Proteins
254 2.3.1 Lysosomal Degradation of Oxidized Proteins and the Role of Autophagy
254 2.3.2 Mitochondrial Degradation of Oxidized Proteins and the Lon Protease
256 2.3.3 The Uptake of Extracellular Oxidized Proteins and the Role of the Proteasome in Their Degradation
258 2.3.4 Calpains and the Degradation of Oxidized Proteins
259 2.4 Role of Heat Shock Proteins in Protein Degradation
260 2.5 Conclusion
262 References
262 3 Protein Oxidation and Aging: Different Model Systems and Affecting Factors 295 3.1 Protein Oxidation during Aging: Lower Organisms and Cellular Model Systems
297 3.1.1 Yeast
297 3.1.1.1 Saccharomyces cerevisiae
297 3.1.1.2 Schizosaccharomyces pombe
301 3.1.2 Podospora anserina
301 3.1.3 Bacteria
302 3.1.3.1 Escherichia coli
302 3.1.4 Cell Cultures
304 3.2 Nonmammalian Model Systems and the Accumulation of Oxidized Proteins during Aging
308 3.2.1 Caenorhabditis elegans
308 3.2.2 Drosophila melanogaster
310 3.2.3 Aquatic Systems
313 3.2.4 Plants
315 3.2.5 Amphibians
317 3.3 Age-Related Protein Oxidation in Humans and Mammals
317 3.3.1 Humans
317 3.3.2 Animals
319 3.3.2.1 Rabbits
323 3.3.2.2 Mice
324 3.3.2.3 Rats
327 3.3.2.4 Gerbils
329 3.3.2.5 Primates
330 3.4 Inherited Factors Influencing Protein Oxidation during Aging
331 3.4.1 Genetic Instability
Mutations
and Polymorphism
331 3.4.2 Gender
333 3.4.3 Vitagenes
334 3.4.4 Signal Transduction and Transcription Factors
335 3.4.5 Ion Channels
340 3.5 Age-Related Protein Aggregate Formation in Model Systems
341 3.6 Environmental Factors Affecting Healthy Aging
342 3.6.1 UV-Induced Skin Photoaging and Skin Aging
344 3.6.2 Pesticides
348 3.6.3 Exercise
349 3.6.4 Dietary Factors and Prevention Strategies
351 3.6.4.1 Melatonin
353 3.6.4.2 Growth Hormone
354 3.6.4.3 Biotrace Metal Elements: Zinc
356 3.6.4.4 Ascorbic Acid
357 3.6.4.5 Vitamin E
360 3.6.4.6 Carnitine and Acetyl-L-Carnitine
361 3.6.4.7 Homocysteine
362 3.6.4.8 Ubiquinone
Coenzyme Q10
363 3.6.4.9 Carnosine
363 3.6.4.10 Lipoic Acid
364 3.6.4.11 N-Acetyl-L-Cysteine
365 3.6.5 Pharmacological Response and Biotransformation in Aging
365 3.6.5.1 Plant Extracts
366 3.6.5.2 Polyphenols and Flavonoids
366 3.6.5.3 Resveratrol
367 3.6.5.4 AGE and ALE Inhibitors
368 3.6.6 Caloric Restriction
369 3.7 Repair and Degradation of Oxidized Proteins during Aging
370 References
372 4 Protein Oxidation in Some Age-Related Diseases 417 4.1 Protein Oxidation during Neurodegeneration and Neurological Diseases
417 4.1.1 Brain Aging
418 4.1.2 Alzheimer's Disease
420 4.1.3 Parkinson's Disease
424 4.1.4 Huntington's Disease
425 4.1.5 Stroke
427 4.1.6 Amyotrophic Lateral Sclerosis
427 4.2 Protein Oxidation in Cardiac Diseases
429 4.2.1 Ischemia-Reperfusion
429 4.2.2 Atherosclerosis
430 4.3 Protein Oxidation in Diabetes
431 4.4 Protein Oxidation in Degenerative Arthritis
434 4.5 Protein Oxidation in Muscle Wasting and Sarcopenia
435 4.6 Protein Oxidation in Destructive Eye Diseases
437 4.6.1 Age-Related Macular Degeneration
437 4.6.2 Cataract
438 4.7 Protein Oxidation in Osteoporosis
440 4.8 Protein Oxidation in Cancer
441 4.8.1 Proteasome Inhibitors in Cancer Therapy
444 4.9 Other Diseases
446 4.9.1 Premature Aging Diseases Progeria and Werner's Syndrome
446 4.9.2 Renal Failure and Hemodialysis in Elderly People
447 4.9.3 Obesity
447 4.9.4 Idiopathic Pulmonary Fibrosis
448 4.9.5 Presbycusis (Age-Related Hear Loss)
448 References
448 List of Abbreviations 479 Index 493
"The format and compartmentalised writing style make this an excellent compendium of knowledge for any researcher interested in assessing our state of knowledge of protein oxidation and ageing. It is easy to find out about the current state of knowledge about a specific reaction, product, method, and/or disease and follow this up by accessing the extensive list of references." -- Chemistry & Industry, 1 July 2013
"With its discussion of current concepts linked to protein oxidation and its impact on aging and the pathology of certain age-related diseases, this book is an important contribution to the field. Students, researchers, scientists, and even clinicians will benefit from it." (Doody's, 10 January 2013)
"The format and compartmentalised writing style make this an excellent compendium of knowledge for any researcher interested in assessing our state of knowledge of protein oxidation and ageing. It is easy to find out about the current state of knowledge about a specific reaction, product, method, and/or disease and follow this up by accessing the extensive list of references." (Chemistry & Industry, 1 July 2013)
"The format and compartmentalised writing style make this an excellent compendium of knowledge for any researcher interested in assessing our state of knowledge of protein oxidation and ageing. It is easy to find out about the current state of knowledge about a specific reaction, product, method, and/or disease and follow this up by accessing the extensive list of references." (Chemistry & Industry, 1 July 2013)