Redox Proteomics

ISABELLA DALLE-DONNE, PHD, is Assistant Professor in the Department of Biology at the University of Milan, Italy. She has a PhD in cellular and molecular biology from the University of Milan. ANDREA SCALONI, PHD, is First Investigator at the Proteomics & Mass Spectrometry Laboratory, ISPAAM, National Research Council in Naples, Italy. He received his PhD in chemical sciences from the University of Rome "La Sapienza" in Italy. D. ALLAN BUTTERFIELD, PHD, is Alumni Professor of Chemistry and Director of the University of Kentucky Center of Membrane Sciences in Lexington, Kentucky, USA. He received his PhD in physical chemistry from Duke University.

Preface xxiii

Contributors xxvii

Part I Oxidatively Modified Proteins and Proteomic Technologies 1

1 Chemical Modification of Proteins by Reactive Oxygen Species 3
Earl R. Stadtman and Rodney L. Levine

1.1 Introduction 3

1.2 Peptide Bond Cleavage 5

1.3 β-Scission 6

1.4 Oxidation of Amino Acid Residue Side Chains 7

2 The Chemistry of Protein Modifications Elicited by Nitric Oxide and Related Nitrogen Oxides 25
Douglas D. Thomas, Lisa Ridnour, Sonia Donzelli, Michael Graham Espey, Daniele Mancardi, Jeffery S. Isenberg, Martin Feelisch, David D. Roberts, and David A. Wink

2.1 Introduction 25

2.2 Chemical Biology of NO 26

2.3 Chemistry of Metabolite Formation 40

3 Mass Spectrometry Approaches for the Molecular Characterization of Oxidatively/Nitrosatively Modified Proteins 59
Andrea Scaloni

3.1 Introduction 59

3.2 Mass Spectrometry Analysis of Oxidatively/Nitrosatively Modified Proteins 61

3.3 Proteomic Strategies for the Identification of ROS/RNS Protein Targets in Biological Matrices 76

3.4 Conclusions 84

4 Thiol-Disulfide Oxidoreduction of Protein Cysteines: Old Methods Revisited for Proteomics 101
Valentina Bonetto and Pietro Ghezzi

4.1 Introduction: Protein Thiols from Oxidative Stress to Redox Regulation 101

4.2 Different Redox States of Protein Cysteines 102

4.3 Methodologies to Identify and Quantify the Redox State of Protein Cysteines 104

4.4 Methods to Detect Specific Modifications 108

4.5 Methods for Enriching Redox-Regulated Proteins 111

4.6 Structural and Physicochemical Determinants for the Susceptibility of Cysteines toward Oxidation 112

4.7 Perspective 114

5 Carbonylated Proteins and Their Implication in Physiology and Pathology 123
Rodney L. Levine and Earl. R. Stadtman

5.1 Introduction 123

5.2 Types of Oxidative Modifications and Choice of Marker 133

5.3 Methodological Considerations 134

5.4 Selected Studies 136

5.5 Carbonylation during Aging 136

6 S-Nitrosation of Cysteine Thiols as a Redox Signal 169
Yanhong Zhang and Neil Hogg

6.1 Introduction 169

6.2 Mechanisms of Formation of S-Nitrosothiols 170

6.3 Cellular Transduction of the S-Nitroso Group 176

6.4 S-Nitrosothiols and Redox Proteomics 178

6.5 S-Nitrosothiols as an Intracellular Signal 179

6.6 Conclusions 182

7 Detection of Glycated and Glyco-Oxidated Proteins 189
Annunziata Lapolla, Elisa Basso, and Pietro Traldi

7.1 Introduction 189

7.2 MALDI-MS in the Study of In vitro Glycated Proteins 196

7.3 MALDI-MS in the Evaluation of Glycation Levels of HSA and IgG in Diabetic Patients 201

7.4 HbA1c and the Real Globin Glycation and Glyco-Oxidation 205

7.5 Determination of Dicarbonyl Compound Levels in Diabetic and Nephropathic Patients 209

7.6 AGE/Peptides: An In vitro Study and In vivo Preliminary Results 212

7.7 Expected Future Trends 226

8 MudPIT (Multidimensional Protein Identification Technology) for Identification of Post-translational Protein Modifications in Complex Biological Mixtures 233
Stefani N. Thomas, Bing-Wen Lu, Tatiana Nikolskaya, Yuri Nikolsky, and Austin J. Yang

8.1 Introduction 233

8.2 Proteomic Analysis of Oxidatively Modified Proteins 234

8.3 Statistical Validation and Interpretation of MudPIT Data 241

8.4 Concluding Remarks 249

9 Use of a Proteomic Technique to Identify Oxidant-Sensitive Thiol Proteins in Cultured Cells 253
Mark B. Hampton, James W. Baty, and Christine C. Winterbourn

9.1 Introduction 253

9.2 Fluorescence Labeling and Proteomic Analysis of Oxidized Thiol Proteins 254

9.3 Detection of Thiol Protein Oxidation in Jurkat Cells 256

9.4 Detection of Reversible and Irreversible Thiol Oxidation 258

9.5 Oxidized Thiol Compared with Reduced Thiol Measurements 259

9.6 More Selective Thiol Labeling Protocols 260

9.7 Identification of Oxidant-Sensitive Proteins 261

9.8 Conclusions and Future Directions 261

10 ICAT (Isotope-Coded Affinity Tag) Approach to Redox Proteomics: Identification and Quantification of Oxidant-Sensitive Protein Thiols 267
Mahadevan Sethuraman, Mark E. McComb, Hua Huang, Sequin Huang, Tyler Heibeck, Catherine E. Costello, and Richard A. Cohen

10.1 Introduction 267

10.2 Oxidant-Sensitive Cys 268

10.3 Challenges in Redox Proteomics 268

10.4 Iodoacetamide-Based Redox Proteomics 269

10.5 ICAT Approach to Redox Proteomics 271

10.6 Validation of the ICAT Approach Using the Recombinant Protein Creatine Kinase 271

10.7 ICAT Approach to the Complex Protein Mixtures 275

10.8 Perspectives 282

11 Quantitative Determination of Free and Protein-Associated 3-Nitrotyrosine and S-Nitrosothiols in the Circulation by Mass Spectrometry and Other Methodologies: A Critical Review and Discussion from the Analytical and Review Point of View 287
Dimitrios Tsikas

11.1 Introduction 287

11.2 Methods of Analysis 295

 

11.3 S-Nitrosothiols and 3-Nitrotyrosine in Health and Disease 314

11.4 Considerations from the Analytical and Review Points of View 326

11.5 Concluding Remarks and Future Prospects 329

Part II Cellular Aspects of Protein Oxidation 343

12 The Covalent Advantage: A New Paradigm for Cell Signaling Mediated by Thiol Reactive Lipid Oxidation Products 345
Dale A. Dickinson, Victor M. Darley-Usmar, and Aimee Landar

12.1 Introduction 345

12.2 Cyclooxygenase and the Conversion of Nonreactive Lipids to Thiol Switching Molecules 346

12.3 Lipid Peroxidation and the Nonenzymatic Formation of Lipid Adducts Capable of Modifying Proteins 349

12.4 The Thiol Switch and Redox Cell Signaling 351

12.5 Biological Responses to Endogenous Electrophilic Lipid Production 353

12.6 A New Paradigm of Oxidized Lipid Signaling—The Covalent Advantage 353

12.7 Implications for the Pathophysiology of Disease 356

12.8 Summary 358

13 Early Molecular Events during Response to Oxidative Stress in Human Cells by Differential Proteomics 369
Gianluca Tell

13.1 Introduction 369

13.2 Cellular Response to Oxidative Stress: From Membrane Receptors to Gene Expression Control 374

13.3 Gene Expression Control during Cell Response to Oxidative Stress: Redox-Regulated Transcription Factors 382

13.4 The Power of Differential Proteomics in Detecting Early Molecular Markers of Oxidative Stress: Examples from Human Cell Lines 383

13.5 Conclusions 388

14 Oxidative Damage to Proteins: Structural Modifications and Consequences in Cell Function 399
Elisa Cabiscol and Joaquim Ros

14.1 Introduction 399

14.2 Glycolysis 400

14.3 Pyruvate Metabolism 426

14.4 Tricarboxylic Acid Cycle 432

14.5 Electron Transport Chain and Oxidative Phosphorylation 437

14.6 Antioxidant Defenses 443

14.7 Molecular Chaperones 447

14.8 Cytoskeleton 451

14.9 Conclusions 454

15 Oxidative Damage and Cellular Senescence: Lessons from Bacteria and Yeast 473
Thomas Nyström

15.1 Microbial Senescence 473

15.2 Protein Carbonylation—An Irreversible Oxidative Damage to Proteins 474

15.3 Bacterial Senescence and Protein Carbonylation 476

15.4 Replicative Senescence and Segregation of Carbonylated Proteins 478

15.5 Yeast Senescence, Protein Oxidation, and Oncogenesis 479

15.6 Perspective 479

Part III Redox Proteomic Analysis in Human Diseases 485

16 Proteins as Sensitive Biomarkers of Human Conditions Associated with Oxidative Stress 487
Isabella Dalle-Donne, Ranieri Rossi, Fabrizio Ceciliani, Daniela Giustarini, Roberto Colombo, and Aldo Milzani

16.1 Introduction 487

16.2 Oxidative Stress in Human Diseases and Animal Models 489

16.3 Biomarkers of Oxidative Stress Status (BOSS) 493

16.4 Proteins as Biomarkers of Oxidative Stress Status 504

16.5 Conclusions 512

17 Degradation and Accumulation of Oxidized Proteins in Age-Related Diseases 527
Peter Voss and Tilman Grune

17.1 Oxidative Modifications of Amino Acids and Protein Damage 527

17.2 Degradation and Accumulation of Oxidatively Modified Proteins 532

17.3 Oxidized Proteins in Age-Related Diseases 543

17.4 Summary 547

18 Redox Proteomics: A New Approach to Investigate Oxidative Stress in Alzheimer’s Disease 563
D. Allan Butterfield, Rukhsana Sultana, and H. Fai Poon

18.1 Introduction 563

18.2 Brain Tissue and Models Used in Studying Aβ(1–42)-Induced Oxidative Stress and Neurotoxicity in AD 565

18.3 Redox Proteomics 567

18.4 Oxidatively Modified Proteins in AD and AD Models by Redox Proteomics 572

18.5 Conclusion 585

19 Oxidized Proteins in Cardiac Ischemia and Reperfusion 605
Jonathan P. Brennan and Philip Eaton

19.1 Introduction to Cardiac Ischemia and Reperfusion 605

19.2 Oxidatively Modified Proteins in the Heart 616

19.3 Established Targets of Post-translational Oxidation 624

19.4 Oxidative Stress in Myocardial Adaptation to Ischemia and Reperfusion 628

19.5 Conclusions, Therapeutic Implications, and Future Directions 631

20 Proteome Analysis of Oxidative Stress: Glutathionyl Hemoglobin in Diabetic and Uremic Patients 651
Toshimitsu Niwa

20.1 Introduction 651

20.2 Glutathionyl Hb as a Marker of Oxidative Stress 653

20.3 Conclusion 663

21 Glyco-oxidative Biochemistry in Diabetic Renal Injury 669
Toshio Miyata

21.1 Presence of Local, but not Generalized, Oxidative Stress in Diabetes 669

21.2 Oxidative Protein Damage In vivo 670

21.3 Antioxidative Properties of Medical Agents 671

21.4 Therapeutic Perspectives for AGE Inhibitors 672

21.5 AGE Inhibition and Renoprotection 673

21.6 Future Prospects 676

22 Quantitative Screening of Protein Glycation, Oxidation, and Nitration Adducts by LC-MS/MS: Protein Damage in Diabetes, Uremia, Cirrhosis, and Alzheimer’s Disease 681
Paul J. Thornalley

22.1 Introduction: Derivatization Free Detection with Application to Modified Proteins and Amino Acids 681

22.2 Physiological Sources of Glycated, Oxidized, and Nitrated Amino Acid Residues and Free Adducts 689

22.3 Protein Glycation and Oxidation in Diabetes: Damage to Cellular and Extracellular Proteins 694

22.4 Profound Mishandling of Glycated, Oxidized, and Nitrated Amino Acids in Uremia 702

22.5 Increased Glycated and Oxidized Amino Acids of Blood Plasma in Liver Cirrhosis—A Signature of Hepatic Oxidative Stress 704

22.6 Increased Methylglyoxal-Derived Hydroimidazolone and 3-Nitrotyrosine Free Adducts in Cerebrospinal Fluid of Subjects with Alzheimer’s Disease—A Signature of Neuronal Damage 707

22.7 Glycation Adducts in Food and Beverages 710

22.8 Concluding Remarks: Physiological Formation and Proteolytic Processing of Glycated, Oxidized, and Nitrated Proteins in Disease Processes—The Importance of Measuring “Damage and Debris” 714

23 Protein Targets and Functional Consequences of Tyrosine Nitration in Vascular Disease 729
Laura M. S. Baker, Bruce A. Freeman, and Mutay Aslan

23.1 Association of Vascular Disease with Increased Production of Reactive Oxygen/Nitrogen Species and Accumulation of Nitrated Proteins 729

23.2 Production of Reactive Oxygen and Nitrogen Species in the Vasculature 731

23.3 Tyrosine Nitration Mechanisms 734

23.4 Methods for Detecting Nitrotyrosine 742

23.5 Selectivity of Tyrosine Nitration 745

23.6 Mechanistic Consequences of Nitrotyrosine Formation: Protein Nitration In vivo and Vascular Disease 747

23.7 Metabolism, Reversibility, and Stability of the Nitrated Tyrosine 764

23.8 Tyrosine Nitration as a Cell Signaling Event 767

23.9 Summary 769

24 Oxidation of Artery Wall Proteins by Myeloperoxidase: A Proteomics Approach 787
Tomas Vaisar and Jay W. Heinecke

24.1 Oxidative Stress in Atherosclerosis 787

24.2 Potential Role of Redox-Active Metal Ions and Glucose in Oxidative Stress 789

24.3 Potential Role of Cellular Pathways in Oxidative Stress 790

24.4 Evidence for Oxidative Modification of LDL in the Human Artery Wall 793

24.5 Oxidative Modification of HDL 796

24.6 Oxidative Regulation of Matrix Metalloproteinases 798

24.7 Conclusions 804

25 Oxidative Stress and Protein Oxidation in Pre-Eclampsia 813
Maarten T. M. Raijmakers, Wilbert H. M. Peters, Christianne J. de Groot, and Eric A. P. Steegers

25.1 Introduction 813

25.2 Oxidative Stress and Pre-Eclampsia 814

25.3 Proteomics 820

26 Involvement of Oxidants in the Etiology of Chronic Airway Diseases: Proteomic Approaches to Identify Redox Processes in Epithelial Cell Signaling and Inflammation 831
Albert van der Vliet, Niki L. Reynaert, Peter F. Bove, Karina Ckless, Anne-Katrin Greul, Milena Hristova, and Yvonne M. Janssen-Heininger

26.1 Introduction 831

26.2 Chronic Airway Inflammation: Conditions Associated with Oxidative and Nitrosative Stress 832

26.3 Biological Significance of Protein Oxidation 836

26.4 Proteomic Approaches to Study Protein Oxidation in Airway Disease 847

26.5 Tissue Proteomics and Application to Study Protein Oxidation 857

26.6 Summary and Conclusions 861

27 Sequestering Agents of Intermediate Reactive Aldehydes as Inhibitors of Advanced Lipoxidation End-Products (ALEs) 877
Marina Carini, Giancarlo Aldini, and Roberto Maffei Facino

27.1 Introduction 877

27.2 Lipoxidation-Derived Reactive Aldehydes 880

27.3 Intervention against Lipoxidation-Derived Carbonyl Stress: ALE Inhibitors 893

27.4 Conclusions and Future Perspective 913

Index 931