TOXI 29 |
| Reactive oxidants and electrophiles derived from lipid oxidation are thought to be mediators of toxic and adaptive responses to oxidative stress. Moreover, protein oxidation products and electrophile adducts may provide markers for oxidative stress associated with environmental exposures and disease processes. We have combined chemical probes and covalent capture strategies to identify protein targets of lipid oxidation-derived electrophiles in human plasma and in cells subjected to treatment with electrophiles or subjected to oxidative stress. Capture strategies have employed 1) biotinylated phospholipids and their oxidation products, 2) Click chemistry to attach biotin tags to azido- or alkynyl-electrophiles and 3) capture of carbonyl-containing electrophile adducts with biotin hydrazide. Shotgun proteome analysis of streptavidin-captured proteins enables identification of target proteins, whereas mapping adduct sites requires novel tandem mass spectrometry approaches. High resolution mass spectrometry is an important tool for characterizing novel adducts and distinguishing between different modifications of nominally similar mass. |
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Frontiers in Chemical Toxicology
1:00 PM-4:45 PM, Monday, August 20, 2007 BCEC -- 258C, Oral
Division of Chemical Toxicology |