Phospholipid oxidation products

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... 

Porter, N. A. and Weenan, H. (1981) High performance liquid chromatographic separation of phospholipids and phospholipid oxidation products, in Methods of Enzymology, Vol. 72, S. P. Colowick and N. O. K. Kaplan, editors, Academic Press, New York, pp. 34-40. 

The Role of Phospholipid Oxidation Products in Inflammatory and Autoimmune Diseases... 

There is extensive evidence that accumulation and subsequent oxidative modification of LDL particles in the subendothelial space play a key role in development and progression of atherosclerosis (Lusis 2000 Berliner et al. 1995 Leitinger 2005). Phospholipid oxidation products are found at high concentrations within fatty streak lesions of cholesterol fed rabbits, mice, and in human atherosclerotic lesions (Watson et al. 1997 Berliner et al. 2001 Subbanagounder et al. 2000 Subbanagounder et al. 2000 Huber et al. 2002). Antibodies against OxPL are present in the serum of apoE-deficient mice and the presence of antibodies against OxPL in patients with atherosclerosis, diabetes, hypertension and other chronic inflammatory diseases further underlines the importance and potential functional relevance of these molecules (Binder et al. 2005). 

These results show that a dyslipidemic microenvironment can directly interfere with DC responses to pathogens and skew the development of T cell-mediated immunity. It will be important to specify the molecular structures within these phospholipid oxidation products that are responsible for their effects on DC function. This will eventually allow designing low molecular substances, which mimic their immunomodulatory effects. 

Berliner, J.A. et al. Evidence for a role of phospholipid oxidation products in atherogenesis. Trends Cardiovasc. Med. 11 (2001) 142-7. 

Bochkov, V.N. et al. Protective role of phospholipid oxidation products in endotoxin-induced tissue damage. Nature 419 (2002a) 77-81. 

Subbanagounder, G. et al. Evidence that phospholipid oxidation products and/or plateletactivating factor play an important role in early atherogenesis in vitro and In vivo inhibition by WEB 2086. Circ. Res. 85 (1999) 311-8. 

Walton, K.A. et al. Specific phospholipid oxidation products inhibit ligand activation of tolllike receptors 4 and 2. Arterioscler. Thromb. Vase. Biol. 23 (2003a) 1197-203. 

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.,... 

Chen, R, Yang, L, and McIntyre, T M, Cytotoxic Phospholipid Oxidation Products Cell Death from Mitochondrial Damage and the Intrinsic Caspase Cascade, J. Biol. Chem. 282 (2007) 24842-24850. 

Porter, N.A. and Weenen, H. 1981. High-performance hquid chromatography separations of phospholipids and phospholipid oxidation products, Meth. EnzymoL, 72, 34. 

Bochkov, V. N., Kadi, A., Huber, J., Gruber, F., Binder, B. R., and Leitinger, N. 2002a. Protective role of phospholipid oxidation products in endotoxin-induced tissue damage. Nature. 419, 77-81. 

Walton, K. A., Cole, A. L., Yeh, M., Subbanagounder, G., Krutzik, S. R., Modlin, R. L., Lucas, R. M. et al. 2003a. Specific phospholipid oxidation products inhibit ligand activation of toll-like receptors 4 and 2. Arterioscler Thromh Va.se Biol. 23, 1197-203. 

Chen, R. Yang, L. McIntyre, T. M., Cytotoxic phospholipid oxidation products. Cell death from mitochondrial damage and the intrinsic caspase cascade. j lChem 2007, 282(34), 24842-50. 

Role for sterol regulatory element-binding protein in activation of endothelial cells by phospholipid oxidation products, 95, 780-788. 

Berliner, J.A. 2006. A role for neutral sphingomyelinase activation in the inhibition of LPS action by phospholipid oxidation products. 47, 1967-1974. 

Another important finding is that mmLDL contains mainly phospholipid oxidation products, while the oxysterol content increases proportionally with the oxidation rate (Shentu et al. 2012). Taken together, these very recent experimental reports and reviews suggest a primary role for oxysterols in the progression of atherosclerosis, rather than in its initiation. However, the marked biochemical changes that oxysterols have been found to bring about in endothelial cells (ECs) suggest that the possibility that cholesterol oxides make some contribution to endothelial dysfunction in atherosclerosis should not be discarded a priori. 

Subbanagounder, G. Leitinger, N. Shih, P.T. Faull, K.F. Berliner, J.A. (1999). Evidence that phospholipid oxidation products and/ or platelet-activating factor play an important role in early atherogenesis in vitro and in vivo inhibition by WEB 2086. Circulation Research, Vol.85, No.4, (August 1999), pp. 311-318, ISSN 1524-4571 Tacon, A.G.J. (2005). Salmon aquaculture dialogue status of information on salmon aquaculture feed and the environment. International Aqua Feed, Vol.8, pp. 22-37, ISSN 1464-0058... 

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