Proteins as biomarkers of oxidative/nitrosative stress in diseases: The contribution of redox proteomics

I. Introduction 00 II. Reactive Oxygen and Nitrogen Species 00 III. Biological Markers of Oxidative/Nitrosative Stress 00 IV. Oxidative/Nitrosative Stress and Protein Modifications 00 A. Oxidative/Nitrosative Modification of Protein Thiols 00 B. Oxidative/Nitrosative Modification of Tyrosine 00 C. Oxidative Modification of Methionine 00 D. Protein Carbonylation 00 E. Oxidative Modification of Histidine and Tryptophan 00 V. MS Approaches for the Molecular Characterization of Oxidatively/Nitrosatively Modified Proteins 00 A. Analysis of Oxidized/Nitrosated Products of Protein Thiols 00 B. Analysis of Oxidized/Nitrated Products of Tyrosine Residues 00 C. Analysis of Oxidized Products of Methionine Residues 00 D. Analysis of Protein Carbonylation Products 00 E. Analysis of Oxidized Products of Tryptophan Residues 00 F. Analysis of Oxidized Products of Histidine Residues 00 VI. Proteomic Strategies for the Identification of ROS/RNS Targets in Complex Protein Mixtures 00 VII. Selected Human Diseases Associated with Oxidative/Nitrosative Stress 00 A. Acute (Adult) Respiratory Distress Syndrome 00 B. Alzheimer's Disease 00 C. Amyotrophic Lateral Sclerosis 00 D. Asthma 00 E. Atherosclerosis 00 F. Chronic Obstructive Pulmonary Diseases 00 G. Diabetes Mellitus 00 H. HIV Infection 00 I. Preeclampsia 00 J. Rheumatoid Arthritis 00 K. Transmissible Spongiform Encephalopathies 00 VIII. Oxidatively Modified Proteins in Human Diseases 00 IX. Concluding Remarks and Future Perspectives 00 Acknowledgments 00 Abbreviations 00 References 00 Reactive oxygen species (ROS) and reactive nitrogen species (RNS) contribute to the pathogenesis and/or progression of several human diseases. Proteins are important molecular signposts of oxidative/nitrosative damage. However, it is generally unresolved whether the presence of oxidatively/nitrosatively modified proteins has a causal role or simply reflects secondary epiphenomena. Only direct identification and characterization of the modified protein(s) in a given pathophysiological condition can decipher the potential roles played by ROS/RNS‐induced protein modifications. During the last few years, mass spectrometry (MS)‐based technologies have contributed in a significant way to foster a better understanding of disease processes. The study of oxidative/nitrosative modifications, investigated by redox proteomics, is contributing to establish a relationship between pathological hallmarks of disease and protei