Introduction

Oxidative stress has been implicated to play an important role in a number of diseases, including neurodegenerative disorders, cancer, and ischemia. Oxidative stress occurs as the result of an imbalance in the pro-oxidants and antioxidant levels. Reactive oxygen species (ROS), which are produced during oxidative stress, can react with proteins, leading to the formation of protein carbonyls. Protein carbonyls are produced by various reactions, including backbone fragmentation, hydrogen atom abstraction at alpha carbons, attack on several amino acid side-chains (Lys, Arg, Pro, Thr, His, etc.), and by the formation of Michael adducts between His, Lys, and Cys residues and reactive alkenals (e.g., 4-hydroxy-2-nonenal;

John T. Hancock (ed.), Methods in Molecular Biology, Redox-Mediated Signal Transduction, vol. 476 © 2008 Humana Press, a part of Springer Science + Business Media, Totowa, NJ DOI: 10.1007/978-1-59745-129-1_11

ref. (1)). Furthermore, the glycation/glycoxidation of Lys amino groups, forming advance glycation end products (1-5), can also lead to the formation of protein carbonyl formation. In addition, a number of reactions of protein radicals can give rise to other radicals, which can cause damage to other bio-molecules, e.g., tyrosine-centered free radicals. Protein oxidation could lead to an impairment of wide range of downstream functional consequences, such as dimerization or aggregation, unfolding or conformational changes to expose more hydro-phobic residues to an aqueous environment, loss of structural or functional activity, alterations in cellular handling/turnover, effects on gene regulation and expression, modulation of cell signaling, induction of apoptosis and necrosis, and the ubiquiti-nylation of damaged or aggregated proteins, indicating that protein oxidation has physiological and pathological significance (1).

Protein carbonyls are chemically stable compared with the other products of oxidative stress. Because of this property, protein carbonyls are widely used as markers to assess the extent of oxidation ofproteins both in in vivo and in vitro conditions (1-3, 5). Several sensitive assays were developed for the detection of oxi-datively modified proteins (3, 6-7). In our laboratory, we use redox proteomics to identify specific carbonylated proteins in the Alzheimer's disease (AD) and models thereof, in addition to other oxidative stress-related diseases (8-19).

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