Oxidized phospholipid signaling: Distress to eustress

Abstract In addition to direct oxidation of proteins by hydrogen peroxide or superoxide, the formation of reactive lipid electrophiles through the process of lipid peroxidation allows an indirect form of signaling, as reactive lipid oxidation products are recognized by a variety of receptors and moreover can form adducts with proteins, thus altering their function. Thus, oxidized lipid products can be perceived as secondary signals. Owing to the wide variety of products of phospholipid oxidation, the biological effects on cells and signaling pathways affected are very diverse. While many proinflammatory effects are considered detrimental and are thought to contribute to disease pathology, a number of anti-inflammatory and protective effects involving antioxidant upregulation are also known. Reactivity of the oxidized lipid products, in terms of their ability to form adducts with proteins, is an important determinant of many of the cellular responses. The catalogue of cellular targets of oxidized lipid products is constantly expanding and partially overlaps with the targets of more direct redox signaling induced by hydrogen peroxide.