LIPID HYDROPEROXIDE GENERATION, TURNOVER, AND EFFECTOR ACTION IN BIOLOGICAL-SYSTEMS

Lipid peroxidation is a well known example of oxidative damage in cell membranes, lipoproteins, and other lipid-containing structures. Perox idative modification of unsaturated phospholipids, glycolipids, and ch olesterol can occur in reactions triggered by i) free radical species such as oxyl radicals, peroxyl radicals, and hydroxyl radicals derived from iron-mediated reduction of hydrogen peroxide or ii) non-radical species such as singlet oxygen, ozone, and peroxynitrite generated by the reaction of superoxide with nitric oxide. Lipid hydroperoxides (LO OHs) are prominent non-radical intermediates of lipid peroxidation who se identification can often provide valuable mechanistic information, e.g., whether a primary reaction is mediated by singlet oxygen or oxyr adicals, Certain cholesterol-derived hydroperoxides (ChOOHs) have been used very effectively in this regard, both in model systems and cells . Being more polar than parent lipids, LOOHs perturb membrane structur e/function and can be deleterious to cells on this basis alone. Howeve r, LOOHs can also participate in redox reactions, the nature and magni tude of which often determines whether peroxidative injury is exacerba ted or prevented. Exacerbation may reflect iron-catalyzed one-electron reduction of LOOHs, resulting in free radical-mediated chain peroxida tion, whereas prevention may reflect selenoperoxidase-catalyzed two-el ectron reduction of LOOHs to relatively non-toxic alcohols. LOOH parti tioning between these two pathways in an oxidatively stressed cell is still poorly understood, but recent cell studies involving various ChO OHs have begun to shed light on this important question. An aspect of related interest that is under intensive investigation is lipid peroxi dation/LOOH-mediated stress signaling, which may evoke a variety of ce llular responses, ranging from induction of antioxidant enzymes to apo ptotic death, Ongoing exploration of these processes will have importa nt bearing on our understanding of disease states associated with pero xidative stress.