Oxidized phospholipids generate

O Donnell, V. B. Murphy, R. C., New families of bioactive oxidized phospholipids generated by inunune cells Identification and signaling actions, 2012, 120(10), 1985-92. 

Catala, A. (2009). Lipid peroxidation of membrane phospholipids generates hydroxy-aUcenals and oxidized phospholipids active in physiological and/or pathological conditions. Chemistry and Physics of Lipids, 157, 1—11. 

Lysophosphatidylcholine is a frequent product of oxidized phospholipid hydrolysis and shows structural similarities to its diacyl counterparts containing a short acyl chain in sn-2 position. Therefore, its cellular activities deserve particular attention, especially in the context of its cytotoxicity. The effects of phospholipid oxidation products and lyso-PC depend not only on their concentration but also on the cell type. Lyso-PC containing a long acyl chain in sn- position (e.g. C16 0, C18 0) is an amphiphilic phospholipid that is generated by phospholipase-catalyzed hydrolysis of phosphatidylcholine or extensive oxidation leading to loss of the entire sn-2 acyl chain. Its critical micellar concentration (CMC) is around 50 pM. It is easily taken up into lipid membranes and increases their fluidities . Above the CMC it forms micelles that destroy membrane integrity also by removal of proteins as shown in erythrocytes (Bierbaum et al., 1979 Colics and Chisholm, 2000). Lyso-PC exerts apoptotic effects in rVSMCs at concentrations below its CMC and induces necrotic cell death at concentrations above its CMC (Hsieh et al.,... 

In recent years most studies on oxidized phospholipids have been performed using mixtures of oxidation products that are generated from their polyunsaturated parent compounds like PA-PC or oxidized lipoprotein particles (e.g. oxLDL). These preparations contain a large variety of different substances differing in structure, polarity and hydrophobicity as well as bioavailability. In many of these oxidized lipid preparations, neither the type nor the content of the individual oxidized components was known. Therefore, the respective compounds contribute to the apparent biological activities of oxidized lipid mixtures to a different and unpredictable extent. Thus, it will be desirable to concentrate on chemically defined lipid species in the future. 

Oxidized phospholipids (OxPLs) have been identified as an active eomponent in minimally modified low-density lipoproteins (LDLs), which is a proinflammatory form of LDL generated by mild oxidation of lipoproteins in the presence of... 

Vitamin E is a natural antioxidant, which occurs in the plasma red cells and tissues, disarms the free radicals, and anticipates the peroxidation of polyunsaturated fatty acids and phospholipids. Also vitamin C is one of the naturally occurring antioxidants, which actually increase the efficiency of vitamin E to avoid the lipid peroxidation. SOD protects the cells of hydrogen peroxide anion free radicals, furnishes the decrease of the catalase which decomposes H2O2, thus yielding a reduction of the oxidative process. This research shows that the EO of Melaleuca armillaris, which has 1,8-cineole as the major chemical compound, can be used as a suppressor for free radicals and is able to avoid damages caused by oxidative stress generated by chemical or physical factors. 

Human serum paraoxonase (PON 1) is an esterase that is physically associated with high-density lipoprotein (HDL) and is also distributed in tissues such as liver, kidney, and intestine [38,39]. Activities of PON 1, which are routinely measured, include hydrolysis of organophosphates, such as paraoxon (the active metabolite of the insecticide parathion) hydrolysis of arylesters, such as phenyl acetate and lactonase activities. Human serum paraoxonase activity has been shown to be inversely related to the risk of cardiovascular disease [40,41], as shown in atherosclerotic, hypercholester-olemic, and diabetic patients [42-44]. In 1998 HDL-associated PON 1 was shown to protect LDL, as well as the HDL particle itself, against oxidation induced by either copper ions or free radical generators [45,46], and this effect could be related to the hydrolysis of the specific lipoproteins oxidized lipids such as cholesteryl linoleate hydroperoxides and oxidized phospholipids. Protection of HDL from oxidation by PON 1 was shown to preserve... 

In 1977, Kellogg and Fridovich [28] showed that superoxide produced by the XO-acetaldehyde system initiated the oxidation of liposomes and hemolysis of erythrocytes. Lipid peroxidation was inhibited by SOD and catalase but not the hydroxyl radical scavenger mannitol. Gutteridge et al. [29] showed that the superoxide-generating system (aldehyde-XO) oxidized lipid micelles and decomposed deoxyribose. Superoxide and iron ions are apparently involved in the NADPH-dependent lipid peroxidation in human placental mitochondria [30], Ohyashiki and Nunomura [31] have found that the ferric ion-dependent lipid peroxidation of phospholipid liposomes was enhanced under acidic conditions (from pH 7.4 to 5.5). This reaction was inhibited by SOD, catalase, and hydroxyl radical scavengers. Ohyashiki and Nunomura suggested that superoxide, hydrogen peroxide, and hydroxyl radicals participate in the initiation of liposome oxidation. It has also been shown [32] that SOD inhibited the chain oxidation of methyl linoleate (but not methyl oleate) in phosphate buffer. 

Several cell lines were used to inveshgate the role of PS oxidahon in apoptosis. Preferenhal oxidahon of PS was observed in human leukemia HL-60 cells (Fabisiak et al, 1998, 2000 Kawai et al, 2000), and normal human keratinocytes (Shvedova et al, 2001). Similarly, in pheochromocytoma PC 12 cells exposed to a radical-generating anhneoplashc dmg, neocarzinostatin, extemalizahon of PS was potentiated by its selechve oxidation in whole cells (Schor et al, 1999). In contrast, this selechve PS oxidahon did not occur in liposomes prepared from mixtures of PnA-labeled phospholipids extracted from the ceUs and exposed to oxidants imder the same conditions (Fabisiak et al, 1998 Kagan et al, 2000 Shvedova et al,... 

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