Protein oxidation - Formation mechanisms, detection and relevance as biomarkers in human diseases

Abstract

Generation of reactive oxygen species and related oxidants is an inevitable consequence of life. Proteins are major targets for oxidation reactions, because of their rapid reaction rates with oxidants and their high abundance in cells, extracellular tissues, and body fluids. Additionally, oxidative stress is able to degrade lipids and carbohydrates to highly reactive intermediates, which eventually attack proteins at various functional sites. Consequently, a wide variety of distinct posttranslational protein modifications is formed by protein oxidation, glycoxidation, and lipoxidation. Reversible modifications are relevant in physiological processes and constitute signaling mechanisms (“redox signaling”), while non-reversible modifications may contribute to pathological situations and several diseases. A rising number of publications provide evidence for their involvement in the onset and progression of diseases as well as aging processes. Certain protein oxidation products are chemically stable and formed in large quantity, which makes them promising candidates to become biomarkers of oxidative damage. Moreover, progress in the development of detection and quantification methods facilitates analysis time and effort and contributes to their future applicability in clinical routine. The present review outlines the most important classes and selected examples of oxidative protein modifications, elucidates the chemistry beyond their formation and discusses available methods for detection and analysis. Furthermore, the relevance and potential of protein modifications as biomarkers in the context of disease and aging is summarized.

Oxidative Stress Biomarkers in Urine of Metal Carpentry Workers Can Be Diagnostic for Occupational Exposure to Low Level of Welding Fumes from Associated Metals

“…While they are always present in human urine samples because of exposure to oxidative stress agents, arising from different sources [7], a dose-response relationship can be used to emphasize the importance of one of them in particular. These oxidation reactions can also affect lipids and proteins; the oxidation of tyrosine leads to the excretion of 3-Nitrotyrosine (3-NO 2 Tyr), one of the most important protein oxidation biomarkers [8]. The methylation product of cytidine, 5-methylcytidine , is an epigenetic marker of RNA damage, and reduced levels of this modified nucleoside are associated with various tumors.…”

The Artemiside-artemisox-artemisone-M1 Tetrad: Efficacies Against Blood Stage P.<em> falciparum</em> Parasites, DMPK Properties, and the Case for Artemiside

“…Methionine sulfoxide is readily reduced by methionine sulfoxide reductase [46,47]. However, further oxidation of methionine sulfoxide provides methionine sulfone that cannot be so reduced [48]. Analogous metabolic transformations are well established for drugs containing sulfide linkages, including cyclic sulfides closely related to those described here [49].…”

Oxidative Crosslinking of Peptides and Proteins: Mechanisms of Formation, Detection, Characterization and Quantification

“…The large body of evidence for di-Tyr crosslinks in oxidized proteins, fluids and tissues; the stability of this species (which is immune to reduction or repair); the association of this crosslink with the onset and development of human pathologies; and advances in analytical methods for the detection and quantification of di-Tyr (see below) have supported its use as a biomarker of protein oxidation in clinical studies [ 144 , 145 ].…”