Oxidized phospholipids: From molecular properties to disease

Abstract

Oxidized lipids are generated from (poly)unsaturated diacyl- and alk(en)ylacyl glycerophospholipids under conditions of oxidative stress. The great variety of reaction products is defined by the degree of modification, hydrophobicity, chemical reactivity, physical properties and biological activity. The biological activities of these compounds may depend on both, the recognition of the particular molecular structures by specific receptors and on the unspecific physical and chemical effects on their target systems (membranes, proteins). In this review, we aim at highlighting the molecular features that are essential for the understanding of the biological actions of pure oxidized phospholipids. Firstly, their chemical structures are described as a basis for an understanding of their physical and (bio)chemical properties in membrane- and protein-bound form. Secondly, the biological activities of oxidized phospholipids are discussed in terms of their unspecific effects on the membrane level as well as their potential interactions with specific targets (receptors) affecting a large set of (signaling) molecules. Finally, the role of oxidized phospholipids as important mediators in pathophysiology is discussed with emphasis on atherosclerosis.

Chronic Alcohol Exposure Increases Circulating Bioactive Oxidized Phospholipids

“…Phospholipid hydroperoxides themselves have no established signaling role, although this may be changing (9), but are relevant because they reflect endogenous oxidative stress and so act as circulating biomarkers of oxidative stress (3). Phospholipid hydroperoxides may also be relevant because they are precursors of a host of oxidatively truncated phospholipids, which are formed by fragmentation of the fatty acyl chain at the site of the (hydro)peroxy function (10), that can be potent inflammatory and apoptotic agonists.…”

Oxidized Phospholipid Inhibition of Toll-like Receptor (TLR) Signaling Is Restricted to TLR2 and TLR4

“…Activated polymorphonuclear cells in particular express enzymes such as NADPH oxidase and myeloperoxidase, which together generate a range of oxidants, including superoxide, hydrogen peroxide, and hypochlorous acid, each of which may be released from these cells to cause oxidative damage not only to invading microorganisms but also to host molecules in surrounding tissues (1). Phospholipids containing polyunsaturated fatty acid chains, such as the abundant phospholipid 1-palmitoyl-2-arachidonyl-sn-glycero-3-phosphorylcholine (PAPC), 2 are particularly susceptible to oxidation by such mediators (2,3), and products of PAPC oxidation have been shown to accumulate at sites of inflammation (3)(4)(5)(6) and in cells treated with stimulants such as IL-1␤, TNF-␣, or long wave ultraviolet radiation (7)(8)(9). Oxidation of PAPC leads to the formation of a mixture of products, ranging from epoxyisoprostanes to truncated chain derivatives that are collectively termed OxPAPC, which is a widely used model for the investigation of oxidized phospholipid (OxPL) function (10 -12).…”

Inflammation-related gene expression by lipid oxidation-derived products in the progression of atherosclerosis

“…Enzymatic or non-enzymatic oxidation of fatty acids linked to the sn-1 and sn-2 positions of glycerophospholipids leads to many different reaction products, depending on chain length and degree of unsaturation [111,163]. These products are implicated as modulators of inflammation, and increased levels of oxPLs are involved in the pathogenesis of various diseases, including atherosclerosis [164][165][166].…”