Lipid peroxidation biomarkers from cellular proteins

TOXI 18

Michelle V. Williams, miwillia@mit.edu1, Peter G. Slade, slade@mit.edu1, John S. Wishnok1, and Steven R. Tannenbaum2. (1) Biological Engineering Division, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 56-731, Cambridge, MA 02139, (2) Biological Engineering Division and Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, 56-731A, Cambridge, MA 02139
The polyunsaturated fatty acyl side chains of phospholipids are extremely sensitive to oxidation, thus providing an excellent source of lipid-derived endogenous toxins. This process of peroxidation has been implicated in the degenerative diseases of aging such as cancer, cardiovascular disease, and neurodegeneration. The prototypic ω-6 lipid hydroperoxide, 13-HPODE, decomposes homolytically to highly reactive α,β-unsaturated aldehydes, such as 9,12-dioxo-10(E)-dodecenoic acid (DODE), 4-oxo-2(E)-nonenal (ONE), 4,5-epoxy-2(E)-decenal (EDE), and 4-hydroxy-2(E)-nonenal (HNE). These products have been shown to damage DNA, RNA, and more recently protein. We previously identified DODE as the most reactive modifier of cytochrome-C in vitro, suggesting that the DODE adduct might serve as a marker for lipid hydroperoxide-mediated macromolecular damage. The goals of our current study are to assess the potential of DODE as a biomarker and to develop a method to selectively purify cellular proteins susceptible to aldehyde/ketone adduct formation from 13-HPODE decomposition.
 

Young Investigator Session
8:15 AM-12:00 PM, Monday, August 20, 2007 BCEC -- 258C, Oral

Division of Chemical Toxicology

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007