ABSTRACT

The investigation of glycerophospholipid (GPL) peroxidation is a rapidly growing field in medicine and biology, encouraged by increasing evidence that lipid oxidation is involved in the pathogenesis of many chronic diseases including atherosclerosis, Alzheimer's disease, Parkinson's disease, stroke, and aging (Spiteller 1998). GPL are major components of biological membranes and lipoproteins. A vast array of aldehydes is produced by oxidative cleavage of polyunsaturated GPL (Esterbauer et al. 1991). The short-chain alkanals and alkenals and their hydroxy or epoxy derivatives have been isolated and fully characterized, including malonaldehyde (MDA), hydroxynonenal, and hydroxyhexenal (Frankel 1982, 1985 and 1999). Much less is known about the nonvolatile products of lipid peroxidation that remain esterified in GPL (Kuksis 1990, Pokorny 1984). Recent studies have shown that oxidative cleavage of the arachidonic acid ester of glycerophosphocholine (GroPCho) generates 5-oxovaleric acid ester of GroPCho, which mimics the plateletactivating factor (PAF) (Stremler et al. 1989 and 1991) that activates endothelial cells to bind monocytes (Watson et al. 1997). Despite the high molecular weight, core aldehydes generated by cleavage of the phospholipids avidly bind covalently with proteins, leading to protein modifications that may interfere with their biological function (Kaur et al. 1997, Kuksis 2000, Ravandi et al. 1997). Covalent binding of the core aldehydes to the apoproteins of both low density (LDL) and high density lipoproteins (HDL) apparently facilitates the entry of monocytes into vascular vessels, an event believed to be important in the development of atherosclerosis (Ahmed et al. 2003b).