Oxidized lipids

Roberts, L. M., Ray, M. J., Shih, T. W., et al., 1997. Strnctnral analy.sis of apolipoprotein A-I Limited proteolysis of methionine-rednced and -oxidized lipid-free and lipid-bonnd human Apo A-I. Biochemistry 36 7615. 

Chin et al. (1992) have su ested that oxidized LDL and high-density lipoprotein (HDL) inactivate endothelial cell-derived NO. NO inactivation was due to the oxidized lipids within the lipoprotein particles and was thought to be explained by a chemical reaction between the lipoproteins and NO. Other investigators have shown that relaxation of vascular smooth muscle by acetylcholine or bradykinin (endothelium-dependent vasodilators) is inhibited by LDL (Andrews etal., 1987). The role of NO in the modification of LDL is discussed in full detail in Chapter 2. 

Evidence that oxidized lipids play a role in the pathogenesis of RA comes from studies demonstrating the presence of lipid products arising from radical attack in rheumatoid synovial fluid. This is consistent with oxidation reactions occurring locally in the joint. Lipid peroxidation products that react with thiobarbituric acid (TBARs) have been detected in rheumatoid knee-joint synovial fluid (Rowley et /., 1984). In addition, the... 

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. 

O Donnell et al. [70] found that LOX and not cyclooxygenase, cytochrome P-450, NO synthase, NADPH oxidase, xanthine oxidase, ribonucleotide reductase, or mitochondrial respiratory chain is responsible for TNF-a-mediated apoptosis of murine fibrosarcoma cells. 15-LOX activity was found to increase sharply in heart, lung, and vascular tissues of rabbits by hypercholesterolemia [71], Schnurr et al. [72] demonstrated that there is an inverse regulation of 12/15-LOXs and phospholipid hydroperoxide glutathione peroxidases in cells, which balanced the intracellular concentration of oxidized lipids. 

The relevance attributed to oxidized lipids, and particularly oxidized LDL, in atherogenesis has precipitated interest in the ability of SERMs to this regard. Ex vivo experiments have confirmed that both tamoxifen and raloxifene exert some protection against the oxidation of LDL particles (Arteaga et al. 2003 Zuckerman and Bryan 1996) and that, interestingly, raloxifene is a more powerful antioxidant than tamoxifen or estradiol. It seems that this antioxidant effect is not mediated by the activation of the ER since pure antiestrogens like ICI 182780 and other SERMs like EM 652 have proven to have similar protective effects on LDL (Hermenegildo et al. 2002) (Fig. 9.4). 

In summary, the binding of oxLDL and/or lipids to several SC receptors (SRAI/II, CD36, CD68) has been clearly demonstrated. Most of other receptors may potentially bind oxLDL or lipids. Consequently, the cellular internalization of oxidized lipids by the SC receptor pathways may be involved in the biological effect of oxLDL, such as apoptosis induction. As a likely major ligand and because of their oxidized lipid contents, oxLDL may have many putative effects on different cells, such as alteration of cell signaling and gene expression. 

Whatever the pathway for oxLDL uptake, numerous observations have demonstrated that their oxidized lipid contents can be directly toxic for the... 

Lipid hydroperoxides and phospholipid oxidation products Lipid hydroperoxides are the major primary products of LDL oxidation. Lipid hydroperoxides (LOOH) are relatively polar, non-radical intermediates of... 

Santanam, N., Auge, N., Zhou, M., Keshava, C., and Parthasarathy, S., 1999, Oveiexpression of human catalase gene decreases oxidized lipid-induced cytotoxicity in vascular smooth muscle cells, Arten osder. Thromb. Vase. Biol. 19 1912-1917. 

HEALTH IMPAIRING OXIDATION PRODUCTS 13.3.1 Oxidized Lipids... 

Oxidation to CO of biodiesel results in the formation of hydroperoxides. The formation of a hydroperoxide follows a well-known peroxidation chain mechanism. Oxidative lipid modifications occur through lipid peroxidation mechanisms in which free radicals and reactive oxygen species abstract a methylene hydrogen atom from polyunsaturated fatty acids, producing a carbon-centered lipid radical. Spontaneous rearrangement of the 1,4-pentadiene yields a conjugated diene, which reacts with molecular oxygen to form a lipid peroxyl radical. 

In the oxidative lipid metabolism, an intermediary a-hydroperoxy acid is formed by a-oxidation of the corresponding fatty acid [82, 83]. Presumably, peroxidase-catalyzed reduction of the hydroperoxide leads to enantiomerically pure (R)-2-hydroxy acids [84]. 

Finally, we conclude that toxic reactions in plant cells injured by ozone probably take place in the following sequence sulfhydryl oxidation, lipid hydrolysis, cellular leaking, lipid peroxidation, and then cellular collapse. 

A correlation may be established between the concentration of oxidized lipids and the TEARS value, expressed as MDA equivalents, in uM units. Correction is due in some cases for the interference by dyes or other factors. For example, the presence of anthocyanins in red cabbage leaves or turbiditjf causes overestimation of lipid hydroperoxides in plant tissue by the TEARS method. TEARS was used to assert the level of endogenous peroxides in hypo- and hyperthyroidism, both conditions being characterized by low lipid and lipoprotein plasma levels and enhanced oxidative metabolism . In a procedure for determination of TEARS in edible oils, the sample is placed in a centrifuge at 12000 g before measuring at 532 nm (e = 1.56 x 10 M cm ) . A usual procedure for determination of TEARS in certain complex matrices involves steam distillation of the aldehydes responsible for the value, instead of extraction. In nitrite-cured meats, excess nitrite may cause nitrosation of MDA, thus interfering with distillation. To avoid this interference sulfanilamide is added, which is converted to a diazonium salt and... 

Xanthine oxidase, which requires Fe, Mo and flavin adenine dinucleotide (FAD) as co-factors, is capable of oxidizing lipids via the production of superoxide radicals. It represents about 20% of the MFGM protein and part is readily lost from the membrane, e.g. on cooling isoelectric focusing... 

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