Redox Proteomes in Human Physiology and Disease Mechanisms

Abstract

Redox proteomics is a field of proteomics that is concerned with the characterization of the oxidation state of proteins to gain information about their modulated structure, function, activity, and involvement in different physiological pathways. Oxidative modifications of proteins have been shown to be implicated in normal physiological processes of cells as well as in pathomechanisms leading to the development of cancer, diabetes, neurodegenerative diseases, and some rare hereditary metabolic diseases, like classic galactosemia. Reactive oxygen species generate a variety of reversible and irreversible modifications in amino acid residue side chains and within the protein backbone. These oxidative post-translational modifications (Ox-PTMs) can participate in the activation of signal transduction pathways and mediate the toxicity of harmful oxidants. Thus the application of advanced redox proteomics technologies is important for gaining insights into molecular mechanisms of diseases. Mass-spectrometry-based proteomics is one of the most powerful methods that can be used to give detailed qualitative and quantitative information on protein modifications and allows us to characterize redox proteomes associated with diseases. This Review illustrates the role and biological consequences of Ox-PTMs under basal and oxidative stress conditions by focusing on protein carbonylation and S-glutathionylation, two abundant modifications with an impact on cellular pathways that have been intensively studied during the past decade.

Extracellular Vesicles under Oxidative Stress Conditions: Biological Properties and Physiological Roles

“…Redox proteomics evidenced, in different tissues, a large number of carbonylated protein species that can affect cellular pathways such as the proteasomal system in different pathological conditions [ 75 , 76 , 77 ]. A different site-specific carbonylation susceptibility across amino acids, and among distinct proteins, has been also demonstrated [ 78 , 79 ].…”

Fluorinated Galactoses Inhibit Galactose-1-Phosphate Uridyltransferase and Metabolically Induce Galactosemia-like Phenotypes in HEK-293 Cells

“…We expect that future studies on these stem cell-like neuronal cells will allow to elucidate more specifically those molecular pathomechanisms associated with developmental changes in the brain of patients suffering from classic galactosemia. One of the major findings of the current study refers to the identification of concertedly affected pathways in galactosemic cells and MIG-HEK293 cells, which both showed a strong response to oxidative stress, a phenomenon that was also revealed in the Drosophila model of classic galactosemia and represents a common feature of various other diseases [28].…”

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

“…This technique facilitates the analysis of specific modifications in a peptide and is also able to determine the modification status of peptides. A prominent example for a labeling approach is the tagging of cysteine to monitor the reversible oxidation status [ 98 , 99 ]. However, more common in standard proteomics are unlabeled methods which have the advantage of less sample manipulation.…”