Detection, identification, and quantification of oxidative protein modifications

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Abstract

Exposure of biological molecules to oxidants is inevitable and therefore commonplace. Oxidative stress in cells arises from both external agents and endogenous processes that generate reactive species, either purposely (e.g. during pathogen killing or enzymatic reactions) or accidentally (e.g. exposure to radiation, pollutants, drugs, or chemicals). As proteins are highly abundant and react rapidly with many oxidants, they are highly susceptible to, and major targets of, oxidative damage. This can result in changes to protein structure, function, and turnover and to loss or (occasional) gain of activity. Accumulation of oxidatively-modified proteins, due to either increased generation or decreased removal, has been associated with both aging and multiple diseases. Different oxidants generate a broad, and sometimes characteristic, spectrum of post-translational modifications. The kinetics (rates) of damage formation also vary dramatically. There is a pressing need for reliable and robust methods that can detect, identify, and quantify the products formed on amino acids, peptides, and proteins, especially in complex systems. This review summarizes several advances in our understanding of this complex chemistry and highlights methods that are available to detect oxidative modifications?at the amino acid, peptide, or protein level?and their nature, quantity, and position within a peptide sequence. Although considerable progress has been made in the development and application of new techniques, it is clear that further development is required to fully assess the relative importance of protein oxidation and to determine whether an oxidation is a cause, or merely a consequence, of injurious process
Original languageEnglish
JournalJournal of Biological Chemistry
Volume294
Issue number51
Pages (from-to)19683-19708
ISSN0021-9258
DOIs
Publication statusPublished - 2019

Keywords

  • oxidative stress
  • oxygen radicals
  • post-translational modification
  • protein chemical modification
  • protein cross-linking
  • carbonyl
  • disulfide
  • hydroperoxide
  • reactive oxygen species

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