Phospholipids in oxidation

Ishii, H. et al. Oxidized phospholipids in oxidized low-density lipoprotein downregulate thrombomodulin transcription in vascular endothelial cells through a decrease in the binding of RAR beta -RXR alpha heterodimers and Spl and 3 to their binding sequences in the TM promoter. Blood 101 (2003) 4767-74. 

Marathe, G.K. et al. Inflammatory platelet-activating factor-like phospholipids in oxidized low density lipoproteins are fragmented alkyl phosphatidylcholines. J. Biol. Chem. 21A (1999) 28395 04. 

Figure 13.8. Formation of hydroperoxides and deeomposition produets from phospholipids in oxidized LDL. Adapted from Navab et al (2004) and Marathe et al (1999). Abbreviations LDL, low-density lipoproteins PAL, palmitoyl ARA, araehidonyl PC, phosphoryleholine Lo, linoleoyl (see Chapters 2 and 3, and Table 13.4).

Marathe, G.K., Davies, S.S., Harrison, K.A., Silva, A.R., Murphy, R.C., Castro-Faria-Neto, H., Prescott, S.M., Zimmerman, G.A. and McIntyre, T.M. Inflammatory platelet-activating factor-hke phospholipids in oxidized low density lipoproteins are fragmented alkyl phosphatidylcholines. J. Biol. Chem. 274, 28395-28404 (1999). 

Choline, a component of the phospholipids in cell membranes, can be prepared by Sn2 reaction of trimethylamine with ethylene oxide. Show the structure of choline, and propose a mechanism for the reaction. 

WOODALL A A, BRITTON G and JACKSON M J (1997) Carotenoids and protection of phospholipids in solution or in liposomes against oxidation by peroxyl radicals relationship between carotenoid structure and protective ability , Biochim Biophys Acta, 1336, 575-86. 

Megli and Sabatini [55] studied the phospholipid bilayers after lipoperoxidation. Phospholipids were oxidized, and the oxidized phospholipid species were separated by PLC and estimated by EPR. It was shown that the early stages of lipoperoxidation brought about disordering of the phospholipid bilayer interior rather than fluidity alterations and that prolonged oxidation may result in a loss of structural and chemical properties of the bilayer until the structure no longer holds. 

Several different tocopherols are known to have vitamin E activity, but a-tocopherol, a trimethyltocol (Figure 12.9) is the most biologically active. Other less potent forms are the /3-, y- and S-tocopherols, which contain fewer methyl groups. They all have antioxidant properties and a deficiency results in a lack of protection of the unsaturated fatty acids in the membrane phospholipids against oxidation by molecular oxygen. 

The fluorophore should be stable under the conditions of measurement. Some fluorophores (e.g., parinaric acid), for example, may be incorporated into phospholipids in natural membranes.(67) Conversely, phospholipids with the fluorophore attached to one of the fatty acyl chains (e.g., DPH-PC) may be cleaved by the action of phospholipases. Also, DPH is susceptible to photobleaching so that a low excitation intensity has to be used. Parinaric acids are liable to oxidize and therefore have to be kept under argon. 

Kagan, V.E., Ritov, V.B., Tyurina, Y.Y., and Tyurin, V.A., 1998, Sensitive and specific florescent probing of oxidative stress in different classes of membrane phospholipids in hve cells using metabolically integrated cw-parinaric add, Meth. Mol. Biol. 108 71-87. 

Lee, H., Shi, W., Tontonoz, P., Wang, S., Subbanagouder, G., Hedrick, C.C., Hama, S., Borromeo, C., Evans, R.M., Berliner, J.A., and Nagy, L, 2000, Role for peroxisome prohferator-activated receptor [alpha] in oxidized phospholipid-induced synthesis of monocyte chematachc protein-1 and interleukin-8 by endothehal cehs, Circ. Res. 87 516-521. 

Role of Nitric Oxide and Membrane Phospholipid Polyunsaturation in Oxidative Cell Death... 

The main action of vitamin E in human tissue is to prevent oxidation of polyunsaturated fatty acids (PUFA), thereby protecting lipid and phospholipids in membranes. Vitamin E interacts syn-ergically with other nutrients, such as vitamin C, selenium, and zinc, which are also involved in the oxidation pathway. The recommended intake is strongly related to the quantity of PUFA consumption. Some studies [454-456] on animal models and epidemiological trials in human suggest... 

Phospholipid classes (see Section V.B.3) may be separated from one another by HPLC-UVD, measuring at 210 nm. Oxidized phospholipids, including hydroperoxide and hydroxy derivatives, can be detected by the same method measuring the signal at 234 nm. This was applied for assessment of the oxidation of phospholipids in human erythrocite membranes catalyzed by soybean lipoxydase in the presence of various modifiers464 506,507. 

Spin trapping has also been applied to the investigation of lipid peroxidation catalysed by myoglobin in linoleate emulsions,204 as well as the oxidation of phospholipids in low-density lipoproteins (18.1) by HOC1.205 Hiramoto et al. have shown that, by quenching the attacking radicals, linoleic acid can protect DNA from oxidation.206 Lipid peroxidation has also been monitored by spin labelling.207... 

Lu, F. S. H., Nielsen, N. S., Timm-Heinrich, M., and Jacobsen, C. (2011). Oxidation stability of marine phospholipids in the liposomal form and their applications. Lipids 46, 3-23. 

Pont, E. G. and Holloway, G. L. 1967. The effect of oxidation on the iodine values of phospholipid in milk, butter and washed-cream serum. J. Dairy Res. 34, 231-238. 

All experiments using lipid membranes employed equal weight ratios of the phospholipid or oxidized phospholipid, and one of the steroids. For the trough experiments, 2 mg of phospholipid and 2 mg of steroid were dissolved In a total of 5 ml of solvent. Hexane was used as the solvent In most Instances, but sma1 1 quantities of chloroform were necessary as a secondary solvent for complete dissolution of the steroid dlol and trlol species. Approximately 0.1 ml of solution was slowly spread on the aqueous sub-phase (consisting of pure water or 0.1 M KC1) In the trough, and the solvent was allowed to completely evaporate before compression experiments were Initiated. Compression was performed slowly In all cases to allow surface equilibration and each sample solution was Investigated at least four times to ensure reproducibility. 

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