Phospholipid hydroperoxides (PLOOHs) arise when unsaturated phospholipids in cell membranes are degraded under conditions of oxidative stress. Such conditions have been correlated with cancer and various other pathological states. If PLOOHs escape detoxification by glutathione-dependent selenoperoxidases (SePXs), they can promote oxidative damage by undergoing iron- catalyzed degradation to free radical species. The hypothesis to be tested is that relatively long-lived PLOOHs, like parent phospholipids, can undergo transfer protein-facilitated movement from one cell membrane to another. No studies relating to this possibility have been reported.
The specific aims of the project are: (1) to investigate facilitated PLOOH transfer in model membrane systems; and (2) to investigate PLOOH toxicity toward leukemia cells and SePX-mediated protection against this. The studies will include (i) isolation/purification of beef liver phosphatidylcholine transfer protein; (ii) photogeneration of PLOOHs in donor membranes; (iii) measurement of peroxide transfer by high performance liquid chromatography with electrochemical detection [HPLC-EC(Hg)]; and (iv) survival measurements on PLOOH/transfer protein-treated cells. These studies are significant because many oxidative stress-induced disorders are attributed to lipid peroxidation and PLOOH transfer may promote this process.
