Mass spectrometry-based methods for identifying oxidized proteins in disease: advances and challenges

Research output: Contribution to journalReview article

Abstract

Many inflammatory diseases have an oxidative aetiology, which leads to oxidative damage to biomolecules, including proteins. It is now increasingly recognized that oxidative post-translational modifications (oxPTMs) of proteins affect cell signalling and behaviour, and can contribute to pathology. Moreover, oxidized proteins have potential as biomarkers for inflammatory diseases. Although many assays for generic protein oxidation and breakdown products of protein oxidation are available, only advanced tandem mass spectrometry approaches have the power to localize specific oxPTMs in identified proteins. While much work has been carried out using untargeted or discovery mass spectrometry approaches, identification of oxPTMs in disease has benefitted from the development of sophisticated targeted or semi-targeted scanning routines, combined with chemical labeling and enrichment approaches. Nevertheless, many potential pitfalls exist which can result in incorrect identifications. This review explains the limitations, advantages and challenges of all of these approaches to detecting oxidatively modified proteins, and provides an update on recent literature in which they have been used to detect and quantify protein oxidation in disease.

LanguageEnglish
Pages378-411
Number of pages34
JournalBiomolecules
Volume5
Issue number2
DOIs
Publication statusPublished - 14 Apr 2015

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Mass spectrometry
Mass Spectrometry
Post Translational Protein Processing
Proteins
Oxidation
Cell signaling
Tandem Mass Spectrometry
Biomolecules
Biomarkers
Pathology
Labeling
Assays
Scanning

Bibliographical note

© 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).

Funding: EPSRC (EP/I017887/1).

Keywords

  • Cardiovascular disease;
  • Chlorotyrosine
  • Inflammation
  • LC-MS/MS
  • Multiple reaction monitoring
  • Neutral loss scanning
  • Nitrotyrosine
  • Oxidative post-translational modification
  • Precursor ion scanning
  • Protein carbonyls

Cite this

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title = "Mass spectrometry-based methods for identifying oxidized proteins in disease: advances and challenges",
abstract = "Many inflammatory diseases have an oxidative aetiology, which leads to oxidative damage to biomolecules, including proteins. It is now increasingly recognized that oxidative post-translational modifications (oxPTMs) of proteins affect cell signalling and behaviour, and can contribute to pathology. Moreover, oxidized proteins have potential as biomarkers for inflammatory diseases. Although many assays for generic protein oxidation and breakdown products of protein oxidation are available, only advanced tandem mass spectrometry approaches have the power to localize specific oxPTMs in identified proteins. While much work has been carried out using untargeted or discovery mass spectrometry approaches, identification of oxPTMs in disease has benefitted from the development of sophisticated targeted or semi-targeted scanning routines, combined with chemical labeling and enrichment approaches. Nevertheless, many potential pitfalls exist which can result in incorrect identifications. This review explains the limitations, advantages and challenges of all of these approaches to detecting oxidatively modified proteins, and provides an update on recent literature in which they have been used to detect and quantify protein oxidation in disease.",
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Mass spectrometry-based methods for identifying oxidized proteins in disease : advances and challenges. / Verrastro, Ivan; Pasha, Sabah; Jensen, Karina Tveen; Pitt, Andrew R.; Spickett, Corinne M.

In: Biomolecules, Vol. 5, No. 2, 14.04.2015, p. 378-411.

Research output: Contribution to journalReview article

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T2 - Biomolecules

AU - Verrastro, Ivan

AU - Pasha, Sabah

AU - Jensen, Karina Tveen

AU - Pitt, Andrew R.

AU - Spickett, Corinne M.

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N2 - Many inflammatory diseases have an oxidative aetiology, which leads to oxidative damage to biomolecules, including proteins. It is now increasingly recognized that oxidative post-translational modifications (oxPTMs) of proteins affect cell signalling and behaviour, and can contribute to pathology. Moreover, oxidized proteins have potential as biomarkers for inflammatory diseases. Although many assays for generic protein oxidation and breakdown products of protein oxidation are available, only advanced tandem mass spectrometry approaches have the power to localize specific oxPTMs in identified proteins. While much work has been carried out using untargeted or discovery mass spectrometry approaches, identification of oxPTMs in disease has benefitted from the development of sophisticated targeted or semi-targeted scanning routines, combined with chemical labeling and enrichment approaches. Nevertheless, many potential pitfalls exist which can result in incorrect identifications. This review explains the limitations, advantages and challenges of all of these approaches to detecting oxidatively modified proteins, and provides an update on recent literature in which they have been used to detect and quantify protein oxidation in disease.

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