Abstract
Oxidative stress has been increasingly implicated in the pathogenesis of a wide variety of diverse human diseases. Free radical damage to lipids, proteins, and DNA may all contribute to the pathogenesis of disease. We have recently discovered a series of highly reactive γ-ketoaldehydes that are formed by rearrangement of bicyclic endperoxide intermediates in the isoprostane (IsoP) pathway of free radical-mediated peroxidation of arachidonic acid (1), which we now term isoketals (IsoKs) (2) (Fig. 1). IsoKs rapidly react with the ε-amine of lysyl residues on proteins to form Schiff base, lactam, and hydroxylactam adducts (1,3,4) (Fig. 2). The rapidity with which IsoKs adduct to proteins exceeds that of other known reactive products of lipid peroxidation, e.g., 4-hydroxynonenal, by orders of magnitude (1). Adduction of proteins frequently leads to altered protein function (5–8). This in turn can lead to cellular dysfunction, which may be causally linked to the pathogenesis of disease processes.
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References
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© 2003 Humana Press Inc.,Totowa, NJ
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Davies, S.S., Brame, C.J., Boutaud, O., Bernoud-Hubac, N., Roberts, L.J. (2003). Measurement of Isoketal Protein Adducts by Liquid Chromatography-Electrospray Ionization/Tandem Mass Spectrometry. In: Hensley, K., Floyd, R.A. (eds) Methods in Biological Oxidative Stress. Methods in Pharmacology and Toxicology. Humana Press. https://doi.org/10.1385/1-59259-424-7:127
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DOI: https://doi.org/10.1385/1-59259-424-7:127
Publisher Name: Humana Press
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