Oxidized phosphatidylcholines

An important characteristic of mammalian 15-LOX is its capacity to oxidize the esters of unsaturated acid in biological membranes and plasma lipoproteins without their hydrolysis to free acids. Jung et al. [19] found that human leukocyte 15-LOX oxidized phosphatidylcholine at carbon-15 of the AA moiety. Soybean and rabbit reticulocyte 15-LOXs were also active while human leukocyte 5-LOX, rat basophilic leukemia cell 5-LOX, and rabbit platelet 12-LOX were inactive. It was suggested that the oxygenation of phospholipid is a unique property of 15-LOX. However, Murray and Brash [20] showed that rabbit reticulocyte... 

As mentioned above, PAF and PAF-like molecules are rapidly synthesized by keratinocytes following UV exposure. We suggest that two mechanisms are involved. UV-induced free radical formation leads to membrane oxidation and the formation of oxidized phosphatidylcholine. The PAF-like molecules bind to PAF receptors in either a paracrine or autocrine fashion. This induces the release of arachidonic acid from the membrane, activates PI.A2 and promotes the synthesis of bona fide PAF.55 The newly synthesized PAF then binds to PAF receptors, which upregulates the production of more PAF and downstream biological modifiers such as eicosanoids and cytokines. Ultimately this activates the cascade of events that leads to immune suppression. 

FIGURE 21-14 Action of plant desaturases. Desaturases in plants oxidize phosphatidylcholine-bound oleate to polyunsaturated fatty acids. Some of the products are released from the phosphatidylcholine by hydrolysis. 

Itabe H, Takeshima E, Iwasaki H, et al. (1994) A monoclonal antibody against oxidized lipoprotein recognizes foam cells in atherosclerotic lesions. Complex formation of oxidized phosphatidylcholines and polypeptides. J Biol Chem 269 15274-15279... 

Qin, J., Goswami, R., Balabanov, R. and Dawson, G. Oxidized phosphatidylcholine is a marker for neuroinflammation in multiple sclerosis brain. J Neurosci Res 85 (2007) 977-984. 

Hazen, S.L. and G.M. Chisohn Oxidized phosphatidylcholines pattern recognition ligands for multiple pathways of the innate immune response. Proc. Natl. Acad. Sci. USA 99 (2002) 12515-7. 

Ikura, Y. et al. Localization of oxidized phosphatidylcholine in nonalcoholic fatty liver disease impact on disease progression. Hepatology 43 (2006) 506-14. 

Fig. 7. Oxidation of LDL phospholipids in the generation of minimally modified LDL. Seeding molecules like HPETE, HPODE, and cholesteryl linoleate hydroperoxide (CE-OOH) are proposed to trigger the oxidation of l-palmitoyl-2-arachidonoyl phosphatidylcholine in LDL, leading to the generation of three oxidized phosphatidylcholine species that confer atherogenic activity to minimally modified LDL. 12-LO, 12-lipoxygenase. Adapted from Ref. [28]. Reproduced with permission from the publisher.

Both circulating OxLDL and MDA-LDL have been measured in plasma by ELISA. Most commonly, the capture antibody is a monoclonal antibody against OxLDL or MDA-LDL and the detection antibody, a polyclonal or monoclonal antibody directed against apo B (El, S12, Tl). Usually, the capture antibody is developed against chemically modified MDA-LDL or OxLDL but antibody has been developed against homogenate of human arteriosclerotic plaque. This antibody reacted with oxidized phosphatidylcholines but not native LDL, or MDA-LDL (S12). 

O Donnell, V. B., Mass spectrometry analysis of oxidized phosphatidylcholine and nhosnhatidvlethanolamine. Biochim Biovhvs Acta 2011. 1811(11), 818-26. 

There is no strict lipid specificity for inhibition of TLRs by OxPLs. Different classes of OxPLs including oxidized phosphatidylcholine, phosphatidylethanol-amine, phosphatidylserine, phosphatidylglycerol, and phosphatidic acid are capable of inhibiting effects of LPS [36,67]. Furthermore, both fragmented OxPLs as well... 

Volinsky, R. and Kinnunen, P.K. 2013. Oxidized phosphatidylcholines in membrane-level cellular signaling From biophysics to physiology and molecular pathology. FEES I, 280, 2806-2816. 

Suppression of Toll-like receptor 4 activation hy endogenous oxidized phosphatidylcholine, KOdiA-PC hy inhibiting LPS binding to MD2. 62, 571-580. 

Yoshimi, N., Ikura, Y, Sugama, Y, Kayo, S., Ohsawa, M., Yamamoto, S., Inoue, Y. et al. 2005. Oxidized phosphatidylcholine in alveolar macrophages in idiopathic interstitial pneumonias, 183, 109-121. 

The oxidation hypothesis that oxidatively modified LDL particles are retained in the intima of arteries leading to atherosclerosis is supported by considerable evidence, but remains unproven. The inflammation hypothesis has recently been emphasized in the mediation of all stages of atherosclerosis including initiation, and acute thrombotic complications of atheroma. Since many lipid oxidation products are pro-inflammatory, the inflammation and oxidation hypotheses are closely linked. Oxidized LDL and the oxidized phosphatidylcholine components of LDL are in fact pro-inflammatory and have proatherogenic properties. In addition to LDL, other lipoprotein particles including VLDL and a subfraction called beta VLDL and IDL may undergo oxidation, activate inflammation and become atherogenic. 

Nakanishi, H., lida, Y., Shimizu, T. and Taguchi, R. (2009) Analysis of oxidized phosphatidylcholines as markers for oxidative stress, using multiple reaction monitoring with theoretically expanded data sets with reversed-phase liquid chromatography/tandem mass spectrometry. J. Chromatogr. B 877, 1366-1374. 

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