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Protein Carbonylation: Principles, Analysis, and Biological Implications

Joaquim Ros (Editor)
ISBN: 978-1-119-07491-5
416 pages
June 2017
Protein Carbonylation: Principles, Analysis, and Biological Implications (1119074916) cover image


Protein carbonylation has attracted the interest of a great number of laboratories since the pioneering studies at the Earl Stadtman’s lab at NIH started in early 1980s. Since then, detecting protein carbonyls in oxidative stress situations became a highly efficient tool to uncover biomarkers of oxidative damage in normal and altered cell physiology.

In this book, research groups from several areas of interest have contributed to update the knowledge regarding detection, analyses and identification of carbonylated proteins and the sites where these modifications occur.

The scientific community will benefit from these reviews since they deal with specific, detailed technical approaches to study formation and detection of protein carbonyls. Moreover, the biological impact of such modifications in metabolic, physiologic and structural functions and, how these alterations can help understanding the downstream effects on cell function are discussed.

  • Oxidative stress occurs in all living organisms and affects proteins and other macromolecules: Protein carbonylation is a measure of oxidative stress in biological systems
  • Mass spectrometry, fluorescent labelling, antibody based detection, biotinylated protein selection and other methods for detecting protein carbonyls and modification sites in proteins are described
  • Aging, neurodegenerative diseases, obstructive pulmonary diseases, malaria, cigarette smoke, adipose tissue and its relationship with protein carbonylation
  • Direct oxidation, glycoxidation and modifications by lipid peroxidation products as protein carbonylation pathways
  • Emerging methods for characterizing carbonylated protein networks and affected metabolic pathways
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Table of Contents

List of Contributors xii

Preface xvi

1 Reactive Oxygen Species Signaling from the Perspective of the Stem Cell 1
Saghi Ghaffari and Raymond Liang

1.1 Introduction 1

1.2 ROS Regulation 2

1.3 ROS Signaling 3

1.4 ROS and Stem Cells 5

1.5 ROS, Metabolism, and Epigenetic Influence 9

1.6 Stem Cells and Mitochondria 9

1.7 ROS and Stem Cell Aging 12

2 Analysis of Protein Carbonylation 24
Ashraf G. Madian, Fred E. Regnier, and Ao Zeng

2.1 Introduction 24

2.2 In Vivo Carbonylation Reactions 27

2.3 Analytical Derivatization of Carbonylated Groups 34

2.4 Selective Purification and/or Detection of Carbonylated Proteins and Peptides 36

2.5 Oxidative Stress ]Based PTMS Not Involving Carbonylation 38

3 Diversity of Protein Carbonylation Pathways: Direct Oxidation,Glycoxidation, and Modifications by Lipid Peroxidation Products 48
Maria Fedorova

3.1 Introduction 48

3.2 Pathways of Protein Carbonylation 49

3.3 Analytical Methods for Detection of Total and Specific Protein Carbonylation 57

3.4 Protein Susceptibility to Different Carbonylation Pathways and Modifications Cross ]Talk 67

4 Protein Carbonylation by Reactive Lipids 83
Koji Uchida

4.1 Introduction 83

4.2 Chemistry of Protein Carbonylation by Reactive Lipid Aldehydes 84

4.3 Antigenicity of Protein Carbonyls 87

4.4 Thiolation of Protein Carbonyls 89

4.5 Reductive Amination ]Based Fluorescent Labeling of Protein Carbonyls 91

5 Mechanism and Functions of Protein Decarbonylation 97
Yuichiro J. Suzuki

5.1 Protein Carbonylation 97

5.2 Primary Protein Carbonylation in Cell Signaling 98

5.3 Discovery and Mechanisms of Protein Decarbonylation 101

5.4 Proposed Functions of Protein Decarbonylation in Oxidative Stress and Redox Signaling 103

6 Carbonylated Proteins and Their Metabolic Regulation: Overview of Mechanisms, Target Proteins, and Characterization Using Proteomic Methods 110
Somaieh Afiuni ]Zadeh and Timothy J. Griffin

6.1 Metabolic Regulation and Reactive Oxygen Species 110

6.2 ROS and Protein Carbonylation 111

6.3 Metabolic Control and Characteristics of Carbonylated Proteins 113

6.4 Protein Targets of Carbonylation and Implications in Human Health 114

6.5 Technologies and Methods for Characterizing Protein Carbonylation 118

6.6 Emerging Multifunctional Reagents for Protein Carbonylation Analysis via MS 119

6.7 Emerging Methods for Characterizing Carbonylated Protein Networks and Affected Pathways 123

7 Oxidative Stress and Protein Carbonylation in Malaria 131
Maria Linares, Antonio Puyet, Amalia Diez, and Jose M. Bautista

7.1 Introduction 131

7.2 Oxidative Stress during Malaria Infection 132

7.3 Protein Carbonylation in Plasmodium and Oxidative Targeting of Antimalarials 137

7.4 Oxidative Dysfunction in Host Tissues 143

7.5 Host Tolerance to Malaria by Modulation of Oxidative Stress Responses 148

7.6 Perspectives 153

8 Protein Carbonylation in Brains of Subjects with Selected Neurodegenerative Disorders 167
Tanea T. Reed and D. Allan Butterfield

8.1 Introduction to Protein Carbonylation 167

8.2 Relationship between ROS and Oxidative Stress 169

8.3 An Overview of Some Neurodegenerative Diseases 171

8.4 Role of Protein Carbonylation in Brains of Subjects with AD 174

8.5 An Introduction to Tauopathies 185

8.6 An Introduction to Amyotrophic Lateral Sclerosis 186

9 Cigarette Smoke ]Induced Protein Carbonylation: Focus on Recent Human Studies 206
Graziano Colombo, Maria Lisa Garavaglia, Aldo Milzani, and Isabella Dalle ]Donne

9.1 Introduction 206

9.2 Protein Carbonylation in Human Smokers 212

9.3 Protein Carbonylation in Cultured Human Cell Models of Exposure to CS 218

9.4 Limitations and Congruence of In Vivo and In Vitro Human Studies 228

10 Chronic Obstructive Pulmonary Disease and Oxidative Damage 241
Esther Barreiro

10.1 Introduction 242

10.2 Protein Oxidation in Tissues 244

10.3 Antioxidants in Skeletal Muscle Fibers 247

10.4 Implications of Protein Carbonylation in COPD Skeletal Muscle Dysfunction 249

10.5 Muscle Protein Carbonylation and Exercise in COPD Patients 252

10.6 Protein Carbonylation in Muscles Exposed to Chronic Cigarette Smoke 253

10.7 Protein Carbonylation in Cancer Cachexia Models 255

10.8 Protein Carbonylation as a Predisposing Mechanism of Lung Cancer in COPD 257

11 Protein Carbonylation in Aging and Senescence 272
Jeannette Konig, Tobias Jung and Tilman Grune

11.1 Introduction 272

11.2 Protein Oxidation during Aging 274

11.3 Chemistry of Protein Carbonylation and Fate of Carbonylated Proteins 277

11.4 Protein Carbonyls in Cellular Aging Models 279

11.5 Protein Carbonylation in Aging Organisms 280

12 Adipose Carbonylation and Mitochondrial Dysfunction 291
Amy K. Hauck, Dalay H. Olson, Joel S. Burrill, and David A. Bernlohr

12.1 Introduction 291

12.2 Reactive Oxygen Species (ROS) 292

12.3 Oxidative Stress and Obesity 298

12.4 Detection of Protein Carbonylation 303

12.5 Outcomes of Protein Carbonylation 306

13 Protein Carbonylation in Plants 321
Ian Max Moller, Jesper F. Havelund, and Adelina Rogowska ]Wrzesinska

13.1 Introduction 322

13.2 Turnover of Reactive Oxygen Species in Plants 323

13.3 Methods Used in Plants for Quantifying and Identifying Carbonylation Sites 325

13.4 Protein Carbonylation in Plants 326

13.5 Protein Carbonylation in Plant Mitochondria 328

13.6 Protein Carbonylation in Seeds 333

14 Specificity of Protein Carbonylation and Its Relevance in Aging 340
Elisa Cabiscol, Jordi Tamarit, and Joaquim Ros

14.1 Introduction 340

14.2 Specificity of Protein Oxidative Damage 341

14.3 Protein Carbonylation in Aging 348

Index 384

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Author Information

Joaquim Ros is Professor at the University of Lleida. From 1995 his research interest has been focused on studying the effect of oxidative stress on proteins in several models (from bacteria to humans) and how this damage affects protein function. He is the head of the Dept. of Basic Medical Sciences, Faculty of Medicine, University of Lleida.

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