Oxidized phospholipids-induced

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. 

Pidkovka, N.A. et al. Oxidized phospholipids induce phenotypic switching of vascular smooth muscle cells in vivo and in vitro. Circ. Res. 101 (2007) 792-801. 

Truncated Oxidized Phospholipids Induce Apoptosis in Vascular Smooth Muscle Cells... 

Fig. 13.3 Signaling pathways involved in oxidized phospholipid-induced apoptosis in mammalian smooth muscle and endothelial cells. AIF, apoptosis inducing factor Apaf-1, apoptosis activating factor 1 aSM, acid sphingomyelinase Az-PC azelaoyl acid ester of lyso-PC Cyt c, cytochrome c G-PC, glutaric acid ester of lyso-PC IM, intermembrane space of the mitochondria JNK, c-Jun N-terminal kinase OV-PC, 5-oxovaleric acid ester of lyso-PC p38, p38 mitogen-activated protein kinase PM, plasma membrane...

Kadi, A. Sharma, P. R. Chen, W. Agrawal, R. Meher, A. K. Rudraiah, S. Grubbs, N. Sharaia, R. Leitinger, N., Oxidized phospholipid-induced inflammation is mediated by Toll-like receptor 2. Free Radio Biol Med 2011, 51(10), 1903-9. 

S. et al. Role for peroxisome proliferator-activated receptor alpha in oxidized phospholipid-induced synthesis of monocyte chemotactic protein-1 and interleukin-8 by endothelial cells. 2000, 87(6), 516-21. 

Cherepanova, O.A., Pidkovka, N.A., Sarmento, O.F., Yoshida, T., Gan, Q., Adiguzel, E., Bendeck, M.P., Berliner, J., Leitinger, N., and Owens, G.K. 2009. Oxidized phospholipids induce type VIII collagen expression and vascular smooth muscle cell migration. 

Kadi, A. et al. Oxidized phospholipid-induced inflammation is mediated by ToU-like receptor 2. Free Radic. Biol. Med. 51, 1903-9, 2011. 

A second important series of experiments dealt with membrane chemistry composed of 5-cho1esten-3B-o1 (cholesterol) and partially oxidized phospholipid. The ultraviolet radiation Induced oxidation led to formation of hydroperoxide moieties at the unsaturated sites on some of the phospholipid acyl chains listed In Table II. The Cjg 2 chain was chosen as a reactive representative... 

Leitinger N., Watson A. D., Faull K. F., Fogelman A. M., and Berliner J. A. (1997). Monocyte binding to endothelial cells induced by oxidized phospholipids present in minimally oxidized low density lipoprotein is inhibited by a platelet activating factor receptor antagonist. Adv. Exp. Med. Biol. 433 379-382. 

Since in all these cases we used oxidants to induce apoptosis, a relatively massive background oxidation of all PnA-labeled phospholipid classes was observed and masked apoptosis-specific PS oxidation. Therefore, we next determined whether a non-oxidant-induced apoptosis model could be used to reveal more explicitly the selective mode of PS oxidation inherent to the apoptosis execution program. To this end, we used agonistic anti-Fas antibody to induce apoptosis in Jurkat B cells according to a commonly used protocol (Fadeel et al., 1999). Importantly, we foundthat anti-Fas-triggered apoptosis in Jurkat cells was characterized by early and selective oxidaiton of cA-PnA-PS (Kagan et al., 2001) without any significant involvement of other classes of phospholipids. 

These results suggest that a GSH deficit significantly contributes to the oxidative stress-induced impairment of membrane phospholipid and mitochondrial function proposed to be involved in the pathophysiology of schizophrenia (Mahadik and Mukherjee, 1996 Mahadik et al., 1998 Yao et al., 1999 Herken et al., 2001 Evans et al., 2003 Marchbanks et al., 2003 Prabakaran et al., 2004). 

On the other hand, the increased GPx activity (possibly via protein synthesis) might be associated with an oxidative stress induced by DHA (22 6, endogenous pool in the course of the DHA (22 6, -3) estoified to tri ycerides is rapidly redistributed within blood lipxqnioteins. The DHA (22 6, w-6) bound and circulate with the albumin fraction not only inhibit platelet aggregation but also influences its uptake into phospholipid species by target tissues (98). DHA therefore seems to impact platelet fatty acid metabolism through unique and novel mechanisms. 

Bluml, S. et al. Oxidized phospholipids negatively regulate dendritic cell maturation induced by TLRs and CD40. J. Immunol. 175 (2005) 501-8. 

Flolzer, G. et al. The dietary soy flavonoid genistein abrogates tissue factor induction in endothelial cells induced by the atherogenic oxidized phospholipid oxPAPC. Thromb. Res. 120 (2007) 71-9. 

Huber, J. et al. Specific monocyte adhesion to endothelial cells induced by oxidized phospholipids involves activation of cPLA2 and lipoxygenase. J. Lipid Res. 47 (2006) 1054-62. 

Huber, J. et al. Oxidized membrane vesicles and blebs from apoptotic cells contain biologically active oxidized phospholipids that induce monocyte-endothelial interactions. Arter-ioscler Thromb VAsc Biol 22 (2002) 101-7. 

Kono, N. et al. Protection against oxidative stress-induced hepatic injury by intracellular type II platelet-activating factor acetylhydrolase by metabolism of oxidized phospholipids in vivo. J. Biol. Chem. 283 (2008) 1628-36. 

Loidl, A. et al. Oxidized phospholipids in minimally modified low density lipoprotein induce apoptotic signaling via activation of acid sphingomyelinase in arterial smooth muscle cells. J Biol Chem. 278 (2003) 32921-8. 

Nonas, S. et al. Oxidized phospholipids reduce ventilator-induced vascular leak and inflammation in vivo. Critical Care, 12(1) R27, 2008. 

Watson, A.D. et al. Structural identification by mass spectrometry of oxidized phospholipids in minimally oxidized low density hpoprotein that induce monocyte/endothelial interactions and evidence for their presence in vivo. J. Biol. Chem. 272 (1997) 13597-607. 

Fig. 13.1 Chemical structures of oxidized phospholipids. (A) Free radical-induced oxidation of l-palmitoyl-2-arachidonoyl-jn-glycero-3-phosphocholine (PA-PC) leads to a plethora of different oxidation products such as peroxidized phospholipids (not shown), truncated phospholipids, isoprostanes, isolevuglandins, and isothromboxanes.

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.,... 

Fruhwirth, G O, Moumtzi, A, Loidl, A, Ingolic, E, and Hermetter, A, The oxidized phospholipids POVPC and PGPC inhibit growth and induce apoptosis in vascular smooth muscle cells, Biochim. Biophys. Acta - Molecular and Cell Biology of Lipids 1761 (2006) 1060-1069. 

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