Abstract
Long thought of as a bystander in pathophysiological processes, lipid molecules have emerged as bioactive mediators of cellular activity. Oxidized phospholipids (OxPLs), generated during enzymatic and non-enzymatic processes, modulate cellular processes through receptor-mediated pathways that can effect a whole host of activities including apoptosis, monocyte adhesion, platelet aggregation, and regulation of immune responses. Initially discovered as platelet activating factor analogs, there have been close to 50 distinct OxPL molecules that have been identified within biological tissues. With the advent of robust analytical systems, we are better able to identify and quantitate these molecules in an ever growing list of different biological tissues which has allowed for the generation of a comprehensive oxolipid profiles in both normal and disease states. Given the increased affinity of phospholipases towards OxPLs we are in the early stages of understanding of the complex interplay between the modification of OxPL through phospholipase activity and the cellular responses to the released hydrolyzed products. In this review we will summarize the role of OxPL in different pathological states and the specific phospholipases that have been shown to interact with OxPLs.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Chisolm G, Steinberg D (2000) The oxidative modification hypothesis of atherogenesis: an overview. Free Radic Biol Med 28:1815–1826
Fessel J, Porter NA, Moore KP et al (2002) Discovery of lipid peroxidation products formed in vivo with a substituted tetrahydrofuran ring (isofurans) that are favored by increased oxygen tension. Proc Natl Acad Sci U S A 99:16713–16718
Weinstein E, Li H, Lawson JA et al (2000) Prothrombinase acceleration by oxidatively damaged phospholipids. J Biol Chem 275:22925–22930
Marathe G et al (2002) Activation of vascular cells by PAF-like lipids in oxidized LDL. Vasc Pharmacol 38(4):193–200
Apel K, Hirt H (2004) Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol 55:373–399
Murphy M (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13
Lenaz G (2001) The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. IUBMB Life 52:159–164
Cour M, Gomez L, Mewton N et al (2011) Postconditioning: from the bench to bedside. J Cardiovasc Pharmacol Ther 16:17–130
Piper H, Meuter K, Schäfer C (2003) Cellular mechanisms of ischemia-reperfusion injury. Ann Thorac Surg 75:8
Crompton M (2000) Mitochondrial intermembrane junctional complexes and their role in cell death. J Physiol 529:11–21
Oskolkova O, Afonyushkin T, Preinerstorfer B et al (2010) Oxidized phospholipids are more potent antagonists of lipopolysaccharide than inducers of inflammation. J Immunol 185:7706–7712
Lambeth J (2002) Nox/Duox family of nicotinamide adenine dinucleotide (phosphate) oxidases. Curr Opin Hematol 9:11–17
Zweier J, Talukder M (2006) The role of oxidants and free radicals in reperfusion injury. Cardiovasc Res 70:181–190
Vinten-Johansen J (2004) Involvement of neutrophils in the pathogenesis of lethal myocardial reperfusion injury. Cardiovasc Res 61:481–497
Frangogiannis N, Smith C, Entman M (2002) The inflammatory response in myocardial infarction. Cardiovasc Res 53:31–47
Schneider C, Porter N, Brash A (2008) Routes to 4-hydroxynonenal: fundamental issues in the mechanisms of lipid peroxidation. J Biol Chem 283:15539–15543
Allen D, Hasanally D, Ravandi A (2013) Role of oxidized phospholipids in cardiovascular pathology. Clin Lipidol 8:205–215
Nonas S, Miller I, Kawkritinarong K et al (2006) Oxidized phospholipids reduce vascular leak and inflammation in rat model of acute lung injury. Am J Respir Crit Care Med 173:1130–1138
Ravandi A, Babaei S, Leung R et al (2004) Phospholipids and oxophospholipids in atherosclerotic plaques at different stages of plaque development. Lipids 39:97–109
Li R, Mouillesseaux KP, Montoya D et al (2006) Identification of prostaglandin E2 receptor subtype 2 as a receptor activated by OxPAPC. Circ Res 98:642–650
Birukova A, Fu P, Chatchavalvanich S et al (2007) Polar head groups are important for barrier-protective effects of oxidized phospholipids on pulmonary endothelium. Am J Physiol Lung Cell Mol Physiol 292:L924–L935
Furukawa M, Gohda T, Tanimoto M, Tomino Y (2013) Pathogenesis and novel treatment from the mouse model of type 2 diabetic nephropathy. Sci World J 2013:928197
Paschos A, Pandya R, Duivenvoorden WC, Pinthus JH (2013) Oxidative stress in prostate cancer: changing research concepts towards a novel paradigm for prevention and therapeutics. Prostate Cancer Prostatic Dis 16:217–225
Tsutsui H, Kinugawa S, Matsushima S (2011) Oxidative stress and heart failure. Am J Physiol Heart Circ Physiol 301:H2181–H2190
Hammond V, Morgan AH, Lauder S et al (2012) Novel keto-phospholipids are generated by monocytes and macrophages, detected in cystic fibrosis, and activate peroxisome proliferator-activated receptor-γ. J Biol Chem 287:41651–41666
Hernandes M, Britto L (2012) NADPH oxidase and neurodegeneration. Curr Neuropharmacol 10:321–327
Wenk M (2010) Lipidomics: new tools and applications. Cell 143:888–895
Han X, Gross R (1994) Electrospray ionization mass spectroscopic analysis of human erythrocyte plasma membrane phospholipids. Proc Natl Acad Sci U S A 91:10635–10639
Nakanishi H, Iida Y, Shimizu T, 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 Analyt Technol Biomed Life Sci 877:1366–1374
Gruber F, Bicker W, Oskolkova OV et al (2012) A simplified procedure for semi-targeted lipidomic analysis of oxidized phosphatidylcholines induced by UVA irradiation. J Lipid Res 53:1232–1242
Quehenberger O, Armando AM, Brown AH et al (2010) Lipidomics reveals a remarkable diversity of lipids in human plasma. J Lipid Res 51:3299–3305
Weir J, Wong G, Barlow CK et al (2013) Plasma lipid profiling in a large population-based cohort. J Lipid Res 54:2898–2908
Andreyev A, Fahy E, Guan Z et al (2010) Subcellular organelle lipidomics in TLR-4-activated macrophages. J Lipid Res 51:2785–2797
Dennis E, Deems RA, Harkewicz R et al (2010) A mouse macrophage lipidome. J Biol Chem 285:39976–39985
White C, Ali A, Hasanally D et al (2013) A cardioprotective preservation strategy employing ex vivo heart perfusion facilitates successful transplant of donor hearts after cardiocirculatory death. J Heart Lung Transplant 32:734–743
Gargalovic P, Imura M, Zhang B et al (2006) Identification of inflammatory gene modules based on variations of human endothelial cell responses to oxidized lipids. Proc Natl Acad Sci U S A 103:12741–12746
Moore K, Sheedy F, Fisher E (2013) Macrophages in atherosclerosis: a dynamic balance. Nat Rev Immunol 13:709–721
Prescott SM, Zimmerman GA, Stafforini DM, McIntyre TM (2000) Platelet-activating factor and related lipid mediators. Annu Rev Biochem 69:419–445
Tyurina YY, Tyurin VA, Zhao Q et al (2004) Oxidation of phosphatidylserine: a mechanism for plasma membrane phospholipid scrambling during apoptosis? Biochem Biophys Res Commun 324:1059–1064
Thomas CP, Morgan LT, Maskrey BH et al (2010) Phospholipid-esterified eicosanoids are generated in agonist-activated human platelets and enhance tissue factor-dependent thrombin generation. J Biol Chem 285:6891–6903
Podrez E, Byzova TV, Febbraio M (2007) Platelet CD36 links hyperlipidemia, oxidant stress and a prothrombotic phenotype. Nat Med 13:1086–1095
Androulakis N, Durand H, Ninio E, Tsoukatos DC (2005) Molecular and mechanistic characterization of platelet-activating factor-like bioactivity produced upon LDL oxidation. J Lipid Res 46:1923–1932
Singleton PA, Chatchavalvanich S, Fu P et al (2009) Akt-mediated transactivation of the S1P1 receptor in caveolin-enriched microdomains regulates endothelial barrier enhancement by oxidized phospholipids. Circ Res 104:978–986
Bochkov V, Oskolkova OV, Birukov KG et al (2010) Generation and biological activities of oxidized phospholipids. Antioxid Redox Signal 12:1009–1059
Weismann D, Binder C (2012) The innate immune response to products of phospholipid peroxidation. Biochim Biophys Acta 1818:2465–2475
Bochkov V (2007) Inflammatory profile of oxidized phospholipids. Thromb Haemost 97:348–354
Zimman A, Mouillesseaux KP, Le T et al (2007) Vascular endothelial growth factor receptor 2 plays a role in the activation of aortic endothelial cells by oxidized phospholipids. Arterioscler Thromb Vasc Biol 27:332–338
Walton K, Hsieh X, Gharavi N et al (2003) Receptors involved in the oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine-mediated synthesis of interleukin-8. A role for Toll-like receptor 4 and a glycosylphosphatidylinositol-anchored protein. J Biol Chem 278:29661–29666
Tsiantoulas D, Gruber S, Binder C (2012) B-1 cell immunoglobulin directed against oxidation-specific epitopes. Front Immunol 3:1–6
Perry H, Bender T, McNamara C (2012) B cell subsets in atherosclerosis. Front Immunol 3:1–11
Binder CJ, Chou MY, Fogelstrand L et al (2008) Natural antibodies in murine atherosclerosis. Curr Drug Targets 9:190–195
Chou MY, Hartvigsen K, Hansen LF et al (2008) Oxidation-specific epitopes are important targets of innate immunity. J Intern Med 263:479–488
Shaw P, Hörkkö S, Chang MK et al (2000) Natural antibodies with the T15 idiotype may act in atherosclerosis, apoptotic clearance, and protective immunity. J Clin Invest 105:1731–1740
Hörkkö S, Bird DA, Miller E et al (1999) Monoclonal autoantibodies specific for oxidized phospholipids or oxidized phospholipid-protein adducts inhibit macrophage uptake of oxidized low-density lipoproteins. J Clin Invest 103:117–128
Chang MK, Binder CJ, Torzewski M et al (2002) C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: phosphorylcholine of oxidized phospholipids. Proc Natl Acad Sci U S A 99:13043–13048
Chang MK, Hartvigsen K, Ryu J et al (2012) The pro-atherogenic effects of macrophages are reduced upon formation of a complex between C-reactive protein and lysophosphatidylcholine. J Inflamm (London, England) 9:42
Boullier A, Friedman P, Harkewicz R et al (2005) Phosphocholine as a pattern recognition ligand for CD36. J Lipid Res 46:969–976
Febbraio M, Hajjar D, Silverstein R (2001) CD36: a class B scavenger receptor involved in angiogenesis, atherosclerosis, inflammation, and lipid metabolism. J Clin Invest 108:785–791
Haserück N, Erl W, Pandey D et al (2004) The plaque lipid lysophosphatidic acid stimulates platelet activation and platelet-monocyte aggregate formation in whole blood: involvement of P2Y1 and P2Y12 receptors. Blood 103:2585–2592
Göpfert MS, Siedler F, Siess W, Sellmayer A (2005) Structural identification of oxidized acyl-phosphatidylcholines that induce platelet activation. J Vasc Res 42:120–132
Berliner J, Leitinger N, Tsimikas S (2009) The role of oxidized phospholipids in atherosclerosis. J Lipid Res 50:S207–S212
Gharavi NM, Baker NA, Mouillesseaux KP et al (2006) Role of endothelial nitric oxide synthase in the regulation of SREBP activation by oxidized phospholipids. Circ Res 98:768–776
Qin J, Testai FD, Dawson S et al (2009) Oxidized phosphatidylcholine formation and action in oligodendrocytes. J Neurochem 110:1388–1399
Yoshida H, Matsui T, Yamamoto A et al (2001) XBP1 mRNA is induced by ATF6 and spliced by IRE1 in response to ER stress to produce a highly active transcription factor. Cell 107:881–891
Dinasarapu RA, Gupta S, Ram Maurya M et al (2013) A combined omics study on activated macrophages—enhanced role of STATs in apoptosis, immunity and lipid metabolism. Bioinformatics (Oxford, England) 2013:1–9
Lartigue L, Faustin B (2013) Mitochondria: metabolic regulators of innate immune responses to pathogens and cell stress. Int J Biochem Cell Biol 45:2052–2056
Chen R, Feldstein A, McIntyre T (2009) Suppression of mitochondrial function by oxidatively truncated phospholipids is reversible, aided by bid, and suppressed by Bcl-XL. J Biol Chem 284:26297–26308
Shih PT, Elices MJ, Fang ZT et al (1999) Minimally modified low-density lipoprotein induces monocyte adhesion to endothelial connecting segment-1 by activating beta1 integrin. J Clin Invest 103:613–625
Vora DK, Fang ZT, Liva SM et al (1997) Induction of P-selectin by oxidized lipoproteins. Separate effects on synthesis and surface expression. Circ Res 80:810–818
Birukova AA, Starosta V, Tian X et al (2013) Fragmented oxidation products define barrier disruptive endothelial cell response to OxPAPC. Transl Res 161:495–504
Kadl A, Galkina E, Leitinger N (2009) Induction of CCR2-dependent macrophage accumulation by oxidized phospholipids in the air-pouch model of inflammation. Arthritis Rheum 60:1362–1371
Furnkranz A, Schober A, Bochkov VN et al (2005) Oxidized phospholipids trigger atherogenic inflammation in murine arteries. Arterioscler Thromb Vasc Biol 25:633–638
Kopf M, Baumann H, Freer G et al (1994) Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368(6469):339–342
Gottlieb RA, Burleson KO, Kloner RA et al (1994) Reperfusion injury induces apoptosis in rabbit cardiomyocytes. J Clin Invest 94:1621–1628
Gustafsson A, Gottlieb R (2003) Mechanisms of apoptosis in the heart. J Clin Immunol 23:447–459
Halestrap A, Kerr PM, Javadov S, Woodfield KY (1998) Elucidating the molecular mechanism of the permeability transition pore and its role in reperfusion injury of the heart. Biochim Biophys Acta 1366:79–94
Chen R, Yang L, McIntyre T (2007) Cytotoxic phospholipid oxidation products. Cell death from mitochondrial damage and the intrinsic caspase cascade. J Biol Chem 282:24842–24850
Fruhwirth G, Moumtzi A, Loidl A et al (2006) The oxidized phospholipids POVPC and PGPC inhibit growth and induce apoptosis in vascular smooth muscle cells. Biochim Biophys Acta 1761:1060–1069
Stemmer U, Dunai ZA, Koller D et al (2012) Toxicity of oxidized phospholipids in cultured macrophages. Lipids Health Dis 11:110
Wallgren M, Lidman M, Pham QD et al (2012) The oxidized phospholipid PazePC modulates interactions between Bax and mitochondrial membranes. Biochim Biophys Acta 1818:2718–2724
Mughal W, Kirshenbaum L (2011) Cell death signalling mechanisms in heart failure. Exp Clin Cardiol 16:102–108
Stremler KE, Stafforini DM, Prescott SM, McIntyre TM (1991) Human plasma platelet-activating factor acetylhydrolase. Oxidatively fragmented phospholipids as substrates. J Biol Chem 266:11095–11103
Bergmark C, Dewan A, Orsoni A et al (2008) A novel function of lipoprotein [a] as a preferential carrier of oxidized phospholipids in human plasma. J Lipid Res 49:2230–2239
Davis B, Koster G, Douet LJ et al (2008) Electrospray ionization mass spectrometry identifies substrates and products of lipoprotein-associated phospholipase A2 in oxidized human low density lipoprotein. J Biol Chem 283:6428–6437
Rivera R, Chun J (2006) Biological effects of lysophospholipids. Rev Physiol Biochem Pharmacol 160:25–46
Salgo MG, Corongiu FP, Sevanian A (1993) Enhanced interfacial catalysis and hydrolytic specificity of phospholipase A2 toward peroxidized phosphatidylcholine vesicles. Arch Biochem Biophys 304:123–132
Tyurin VA, Yanamala N, Tyurina YY et al (2012) Specificity of lipoprotein-associated phospholipase A(2) toward oxidized phosphatidylserines: liquid chromatography-electrospray ionization mass spectrometry characterization of products and computer modeling of interactions. Biochemistry 51:9736–9750
Kokotos G, Hsu YH, Burke JE et al (2010) Potent and selective fluoroketone inhibitors of group VIA calcium-independent phospholipase A2. J Med Chem 53:3602–3610
Dennis E, Cao J, Hsu YH et al (2011) Phospholipase A2 enzymes: physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention. Chem Rev 111:6130–6185
Code C, Mahalka AK, Bry K, Kinnunen PK (2010) Activation of phospholipase A2 by 1-palmitoyl-2-(9′-oxo-nonanoyl)-sn-glycero-3-phosphocholine in vitro. Biochim Biophys Acta 1798:1593–1600
Cordella-Miele E, Miele L, Mukherjee A (1990) A novel transglutaminase-mediated post-translational modification of phospholipase A2 dramatically increases its catalytic activity. J Biol Chem 265:17180–17188
Samoilova EV, Pirkova AA, Prokazova NV, Korotaeva AA (2010) Effects of LDL lipids on activity of group IIA secretory phospholipase A2. Bull Exp Biol Med 150:39–41
Koumanov K, Wolf C, Béreziat G (1997) Modulation of human type II secretory phospholipase A2 by sphingomyelin and annexin VI. Biochem J 326:227–233
Korotaeva AA, Samoilova EV, Piksina GF, Prokazova NV (2010) Oxidized phosphatidylcholine stimulates activity of secretory phospholipase A2 group IIA and abolishes sphingomyelin-induced inhibition of the enzyme. Prostaglandins Other Lipid Mediat 91:38–41
Korotaeva A, Samoilova E, Pavlunina T, Panasenko OM (2013) Halogenated phospholipids regulate secretory phospholipase A2 group IIA activity. Chem Phys Lipids 167–168:51–56
Pucer A, Brglez V, Payre C et al (2013) Group X secreted phospholipase A2 induces lipid droplet formation and prolongs breast cancer cell survival. Mol Cancer 12:111
Murph M, Tanaka T, Pang J et al (2007) Liquid chromatography mass spectrometry for quantifying plasma lysophospholipids: potential biomarkers for cancer diagnosis. Methods Enzymol 433:1–25
Moses G, Jensen MD, Lue LF et al (2006) Secretory PLA2-IIA: a new inflammatory factor for Alzheimer’s disease. J Neuroinflammation 3:28
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2014 Springer Science+Business Media New York
About this chapter
Cite this chapter
Hasanally, D., Chaudhary, R., Ravandi, A. (2014). Role of Phospholipases and Oxidized Phospholipids in Inflammation. In: Tappia, P., Dhalla, N. (eds) Phospholipases in Health and Disease. Advances in Biochemistry in Health and Disease, vol 10. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-0464-8_3
Download citation
DOI: https://doi.org/10.1007/978-1-4939-0464-8_3
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4939-0463-1
Online ISBN: 978-1-4939-0464-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)