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Keywords:

  • biological markers;
  • mass spectrometry;
  • methionine sulfoxide;
  • nitrosothiols;
  • nitrotyrosine;
  • protein carbonylation;
  • protein oxidation;
  • proteomics;
  • reactive nitrogen species;
  • reactive oxygen species;
  • S-glutathionylation;
  • S-nitrosation

Abstract

  I.Introduction00
 II.Reactive Oxygen and Nitrogen Species00
 III.Biological Markers of Oxidative/Nitrosative Stress00
 IV.Oxidative/Nitrosative Stress and Protein Modifications00
 A.  Oxidative/Nitrosative Modification of Protein Thiols00
 B.  Oxidative/Nitrosative Modification of Tyrosine00
 C.  Oxidative Modification of Methionine00
 D.  Protein Carbonylation00
 E.  Oxidative Modification of Histidine and Tryptophan00
  V.MS Approaches for the Molecular Characterization of Oxidatively/Nitrosatively Modified Proteins00
 A.  Analysis of Oxidized/Nitrosated Products of Protein Thiols00
 B.  Analysis of Oxidized/Nitrated Products of Tyrosine Residues00
 C.  Analysis of Oxidized Products of Methionine Residues00
 D.  Analysis of Protein Carbonylation Products00
 E.  Analysis of Oxidized Products of Tryptophan Residues00
 F.  Analysis of Oxidized Products of Histidine Residues00
  VI.Proteomic Strategies for the Identification of ROS/RNS Targets in Complex Protein Mixtures00
 VII.Selected Human Diseases Associated with Oxidative/Nitrosative Stress00
 A.  Acute (Adult) Respiratory Distress Syndrome00
 B.  Alzheimer's Disease00
 C.  Amyotrophic Lateral Sclerosis00
 D.  Asthma00
 E.  Atherosclerosis00
 F.  Chronic Obstructive Pulmonary Diseases00
 G.  Diabetes Mellitus00
 H.  HIV Infection00
 I.  Preeclampsia00
 J.  Rheumatoid Arthritis00
 K.  Transmissible Spongiform Encephalopathies00
 VIII.Oxidatively Modified Proteins in Human Diseases00
  IX.Concluding Remarks and Future Perspectives00
Acknowledgments00
Abbreviations00
References00

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 protein structural and functional abnormalities. MS-based technologies promise a contribution in a new era of molecular medicine, especially in the discovery of diagnostic biomarkers of oxidative/nitrosative stress, enabling early detection of diseases. Indeed, identification and characterization of oxidatively/nitrosatively modified proteins in human diseases has just begun. © 2004 Wiley Periodicals, Inc., Mass Spec Rev