Redox-dependent anti-inflammatory signaling actions of unsaturated fatty acids

Annual Review of Physiology

Volumn 76, Issue , 2014, Pages 79-105

  Delmastro Greenwood, Meghan ^a   Freeman, Bruce A ^a   Wendell, Stacy Gelhaus ^a  

^a UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

Author keywords

, unsaturated carbonyl; Electrophiles; Michael acceptors; Nitro fatty acid; Therapeutics

Indexed keywords

ANIMALS; ANTI-INFLAMMATORY AGENTS; EPOXY COMPOUNDS; FATTY ACIDS; FATTY ACIDS, UNSATURATED; FREE RADICALS; HUMANS; KETO ACIDS; NITRO COMPOUNDS; OXIDATION-REDUCTION; PROSTAGLANDINS; SIGNAL TRANSDUCTION;

EID: 84894119906     PISSN: 00664278     EISSN: 15451585     Source Type: Book Series    
DOI: 10.1146/annurev-physiol-021113-170341     Document Type: Review

References (161)

1. Singh J, Petter RC, Baillie TA, Whitty A. 2011. The resurgence of covalent drugs. Nat. Rev. Drug Discov. 10:307-177
2. Bottcher C, Pollmann S. 2009. Plant oxylipins: plant responses to 12-oxo-phytodienoic acid are governed by its specific structural and functional properties. FEBS J. 276:4693-7044
3. Gersch M, Kreuzer J, Sieber SA. 2012. Electrophilic natural products and their biological targets. Nat. Prod. Rep. 29:659-822
4. Lands B. 2012. Consequences of essential fatty acids. Nutrients 4:1338-577
5. Singer P, Shapiro H, Theilla M, Anbar R, Singer J, Cohen J. 2008. Anti-inflammatory properties of omega-3 fatty acids in critical illness: novel mechanisms and an integrative perspective. Intensiv. Care Med. 34:1580-922
6. Churruca I, Fernandez-Quintela A, Portillo MP. 2009. Conjugated linoleic acid isomers: differences in metabolism and biological effects. Biofactors 35:105-111
7. Woodcock SR, Bonacci G, Gelhaus SL, Schopfer FJ. 2013. Nitrated fatty acids: synthesis and measurement. Free Radic. Biol. Med. 59:14-266
8. Garzon B, Oeste CL, Diez-Dacal B, Perez-Sala D. 2011. Proteomic studies on protein modification by cyclopentenone prostaglandins: expanding our view on electrophile actions. J. Proteomics 74:2243-633
9. Suzuki M, Mori M, Niwa T, Hirata R, Furuta R, et al. 1997. Chemical implications for antitumor and antiviral prostaglandins: reaction of 7-prostaglandin A1 and prostaglandin A1 methyl esters with thiols. J. Am. Chem. Soc. 119:2376-855
10. Yin H, Xu L, Porter NA. 2011. Free radical lipid peroxidation: mechanisms and analysis. Chem. Rev. 111:5944-722
11. Schopfer FJ, Cipollina C, Freeman BA. 2011. Formation and signaling actions of electrophilic lipids. Chem. Rev. 111:5997-60211
12. Lundberg JO, Weitzberg E. 2013. Biology of nitrogen oxides in the gastrointestinal tract. Gut 62:616-299
13. Trostchansky A, Bonilla L, Gonzalez-Perilli L, Rubbo H. 2013. Nitro-fatty acids: formation, redox signaling, and therapeutic potential. Antioxid. Redox Signal. 19(11):1257-655
14. Bonacci G, Baker PR, Salvatore SR, Shores D, Khoo NK, et al. 2012. Conjugated linoleic acid is a preferential substrate for fatty acid nitration. J. Biol. Chem. 287:44071-822
15. Bochkov VN, Oskolkova OV, Birukov KG, Levonen AL, Binder CJ, Stockl J. 2010. Generation and biological activities of oxidized phospholipids. Antioxid. Redox Signal. 12:1009-599
16. Upston JM, Neuzil J, Witting PK, Alleva R, Stocker R. 1997. Oxidation of free fatty acids in low density lipoprotein by 15-lipoxygenase stimulates nonenzymic, tocopherol-mediated peroxidation of cholesteryl esters. J. Biol. Chem. 272:30067-744
17. Upston JM,Witting PK, Brown AJ, Stocker R, Keaney JF Jr. 2001. Effect of vitamin E on aortic lipid oxidation and intimal proliferation after arterial injury in cholesterol-fed rabbits. Free Radic. Biol. Med. 31:1245-533
18. Witting PK, Mohr D, Stocker R. 1999. Assessment of prooxidant activity of vitamin E in human low-density lipoprotein and plasma. Methods Enzymol. 299:362-755
19. Pratt DA, Mills JH, Porter NA. 2003. Theoretical calculations of carbon-oxygen bond dissociation enthalpies of peroxyl radicals formed in the autoxidation of lipids. J. Am. Chem. Soc. 125:5801-100
20. Porter NA,Wolf RA, Yarbro EM,Weenen H. 1979. The autoxidation of arachidonic acid: formation of the proposed SRS-A intermediate. Biochem. Biophys. Res. Commun. 89:1058-644
21. HambergM, Svensson J, Samuelsson B. 1974. Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins. Proc. Natl. Acad. Sci. USA 71:3824-288
22. Shibata T, Kondo M, Osawa T, Shibata N, Kobayashi M, Uchida K. 2002. 15-Deoxy-12,14-prostaglandin J2. A prostaglandin D2 metabolite generated during inflammatory processes. J. Biol. Chem. 277:10459-666
23. Ziboh VA, Miller CC, Cho Y. 2000. Metabolism of polyunsaturated fatty acids by skin epidermal enzymes: generation of antiinflammatory and antiproliferative metabolites. Am. J. Clin. Nutr. 71:S361-666
24. Hardy KD, Cox BE, Milne GL, Yin H, Roberts LJ 2nd. 2011. Nonenzymatic free radical-catalyzed generation of 15-deoxy-12,14-prostaglandin J2-like compounds (deoxy-J2-isoprostanes) in vivo. J. Lipid Res. 52:113-244
25. Bickley JF, Ciucci A, Evans P, Roberts SM, Ross N, Santoro MG. 2004. Reactions of some cyclopentenones with selected cysteine derivatives and biological activities of the product thioethers. Bioorg. Med. Chem. 12:3221-277
26. Narumiya S, FukushimaM. 1986. Site and mechanism of growth inhibition by prostaglandins. I. Active transport and intracellular accumulation of cyclopentenone prostaglandins, a reaction leading to growth inhibition. J. Pharmacol. Exp. Ther. 239:500-55
27. Narumiya S, Ohno K, Fujiwara M, Fukushima M. 1986. Site and mechanism of growth inhibition by prostaglandins. II. Temperature-dependent transfer of a cyclopentenone prostaglandin to nuclei. J. Pharmacol. Exp. Ther. 239:506-111
28. Gutierrez J, Ballinger SW, Darley-Usmar VM, Landar A. 2006. Free radicals, mitochondria, and oxidized lipids: the emerging role in signal transduction in vascular cells. Circ. Res. 99:924-322
29. Paumi CM, Wright M, Townsend AJ, Morrow CS. 2003. Multidrug resistance protein (MRP) 1 and MRP3 attenuate cytotoxic and transactivating effects of the cyclopentenone prostaglandin, 15-deoxy-12,14prostaglandin J2 in MCF7 breast cancer cells. Biochemistry 42:5429-377
30. Yu X, Egner PA, Wakabayashi J, Wakabayashi N, Yamamoto M, Kensler TW. 2006. Nrf2-mediated induction of cytoprotective enzymes by 15-deoxy-12,14- prostaglandin J2 is attenuated by alkenal/one oxidoreductase. J. Biol. Chem. 281:26245-522
31. Mesaros C, Lee SH, Blair IA. 2009. Targeted quantitative analysis of eicosanoid lipids in biological samples using liquid chromatography-tandem mass spectrometry. J. Chromatogr. B 877:2736-455
32. Bronstein JC, Bull AW. 1997. Substrate specificity and characterization of partially purified rat liver 13-hydroxyoctadecadienoic acid (13-HODE) dehydrogenase. Arch. Biochem. Biophys. 348:219-255
33. Erlemann KR, Cossette C, Grant GE, Lee GJ, Patel P, et al. 2007. Regulation of 5-hydroxyeicosanoid dehydrogenase activity in monocytic cells. Biochem. J. 403:157-655
34. Na HK, Park JM, Lee HG, Lee HN, Myung SJ, Surh YJ. 2011. 15-Hydroxyprostaglandin dehydrogenase as a novel molecular target for cancer chemoprevention and therapy. Biochem. Pharmacol. 82:1352-600
35. Murphy RC, Zarini S. 2002. Glutathione adducts of oxyeicosanoids. Prostaglandins Other Lipid Mediat. 68-69:471-822
36. Wei C, Zhu P, Shah SJ, Blair IA. 2009. 15-oxo-Eicosatetraenoic acid, a metabolite of macrophage 15-hydroxyprostaglandin dehydrogenase that inhibits endothelial cell proliferation. Mol. Pharmacol. 76:516-255
37. Liu X, Zhang S, Arora JS, Snyder NW, Shah SJ, Blair IA. 2011. 11-Oxoeicosatetraenoic acid is a cyclooxygenase-2/15-hydroxyprostaglandin dehydrogenase-derived antiproliferative eicosanoid. Chem. Res. Toxicol. 24:2227-366
38. Groeger AL, Cipollina C, Cole MP, Woodcock SR, Bonacci G, et al. 2010. Cyclooxygenase-2 generates anti-inflammatory mediators from omega-3 fatty acids. Nat. Chem. Biol. 6:433-411
39. Serhan CN, Petasis NA. 2011. Resolvins and protectins in inflammation resolution. Chem. Rev. 111:5922-433
40. Imig JD. 2012. Epoxides and soluble epoxide hydrolase in cardiovascular physiology. Physiol. Rev. 92:101-300
41. Morisseau C, Hammock BD. 2013. Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu. Rev. Pharmacol. Toxicol. 53:37-588
42. Arnold C, Markovic M, Blossey K,Wallukat G, Fischer R, et al. 2010. Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of 3 fatty acids. J. Biol. Chem. 285:32720-333
43. Konkel A, SchunckWH. 2011. Role of cytochrome P450 enzymes in the bioactivation of polyunsaturated fatty acids. Biochim. Biophys. Acta 1814:210-222
44. Gardner HW, Jursinic PA. 1981. Degradation of linoleic acid hydroperoxides by a cysteine. FeCl3 catalyst as a model for similar biochemical reactions. I. Study of oxygen requirement, catalyst and effect of pH. Biochim. Biophys. Acta 665:100-122
45. Gardner HW, Kleiman R. 1981. Degradation of linoleic acid hydroperoxides by a cysteine. FeCl3 catalyst as a model for similar biochemical reactions. II. Specificity in formation of fatty acid epoxides. Biochim. Biophys. Acta 665:113-244
46. Bruder ED, Ball DL, Goodfriend TL, Raff H. 2003. An oxidized metabolite of linoleic acid stimulates corticosterone production by rat adrenal cells. Am. J. Physiol. Regul. Integr. Comp. Physiol. 284:R1631-355
47. Chawengsub Y, Gauthier KM, Nithipatikom K, Hammock BD, Falck JR, et al. 2009. Identification of 13-hydroxy-14,15-epoxyeicosatrienoic acid as an acid-stable endothelium-derived hyperpolarizing factor in rabbit arteries. J. Biol. Chem. 284:31280-900
48. Serhan CN, Fredman G, Yang R, Karamnov S, Belayev LS, et al. 2011. Novel proresolving aspirintriggered DHA pathway. Chem. Biol. 18:976-877
49. Batthyany C, Schopfer FJ, Baker PR, Duran R, Baker LM, et al. 2006. Reversible post-translational modification of proteins by nitrated fatty acids in vivo. J. Biol. Chem. 281:20450-633
50. Lin D, Saleh S, Liebler DC. 2008. Reversibility of covalent electrophile-protein adducts and chemical toxicity. Chem. Res. Toxicol. 21:2361-699
51. Rudolph TK, Freeman BA. 2009. Transduction of redox signaling by electrophile-protein reactions. Sci. Signal. 2:re77
52. Rudolph V, Schopfer FJ, Khoo NK, Rudolph TK, ColeMP, et al. 2009. Nitro-fatty acid metabolome: saturation, desaturation, β-oxidation, and protein adduction. J. Biol. Chem. 284:1461-733
53. Kensler TW, Wakabayashi N, Biswal S. 2007. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway. Annu. Rev. Pharmacol. Toxicol. 47:89-1166
54. Kansanen E, Kivela AM, Levonen AL. 2009. Regulation of Nrf2-dependent gene expression by 15-deoxy-12,14-prostaglandin J2. Free Radic. Biol. Med. 47:1310-177
55. Kobayashi A, Kang MI, Watai Y, Tong KI, Shibata T, et al. 2006. Oxidative and electrophilic stresses activate Nrf2 through inhibition of ubiquitination activity of Keap1. Mol. Cell. Biol. 26:221-299
56. Rachakonda G, Xiong Y, Sekhar KR, Stamer SL, Liebler DC, Freeman ML. 2008. Covalent modification at Cys151 dissociates the electrophile sensor Keap1 from the ubiquitin ligase CUL3. Chem. Res. Toxicol. 21:705-100
57. Kobayashi M, Li L, Iwamoto N, Nakajima-Takagi Y, Kaneko H, et al. 2009. The antioxidant defense system Keap1-Nrf2 comprises amultiple sensing mechanism for responding to a wide range of chemical compounds. Mol. Cell. Biol. 29:493-5022
58. Kansanen E, Bonacci G, Schopfer FJ, Kuosmanen SM, Tong KI, et al. 2011. Electrophilic nitro-fatty acids activate NRF2 by a KEAP1 cysteine 151-independent mechanism. J. Biol. Chem. 286:14019-277
59. He X, Ma Q. 2009. NRF2 cysteine residues are critical for oxidant/electrophile-sensing, Kelch-like ECH-associated protein-1-dependent ubiquitination-proteasomal degradation, and transcription activation. Mol. Pharmacol. 76:1265-788
60. Tsujita T, Li L, Nakajima H, Iwamoto N, Nakajima-Takagi Y, et al. 2011. Nitro-fatty acids and cyclopentenone prostaglandins share strategies to activate the Keap1-Nrf2 system: a study using green fluorescent protein transgenic zebrafish. Genes Cells 16:46-577
61. Wright MM, Schopfer FJ, Baker PR, Vidyasagar V, Powell P, et al. 2006. Fatty acid transduction of nitric oxide signaling: Nitrolinoleic acid potently activates endothelial heme oxygenase 1 expression. Proc. Natl. Acad. Sci. USA 103:4299-3044
62. Villacorta L, Zhang J, Garcia-Barrio MT, Chen XL, Freeman BA, et al. 2007. Nitro-linoleic acid inhibits vascular smooth muscle cell proliferation via the Keap1/Nrf2 signaling pathway.Am. J. Physiol. Heart Circ. Physiol. 293:H770-766
63. Kansanen E, Jyrkkanen HK, Volger OL, Leinonen H, Kivela AM, et al. 2009. Nrf2-dependent and -independent responses to nitro-fatty acids in human endothelial cells: identification of heat shock response as the major pathway activated by nitro-oleic acid. J. Biol. Chem. 284:33233-411
64. Cole MP,Rudolph TK,KhooNK, MotanyaUN, Golin-Bisello F, et al. 2009. Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury. Circ. Res. 105:965-722
65. Ferreira AM, Ferrari MI, Trostchansky A, Batthyany C, Souza JM, et al. 2009. Macrophage activation induces formation of the anti-inflammatory lipid cholesteryl-nitrolinoleate. Biochem. J. 417:223-344
66. Wright MM, Kim J,Hock TD, LeitingerN, Freeman BA, Agarwal A. 2009. Human haem oxygenase-1 induction by nitro-linoleic acid is mediated by cAMP, AP-1 and E-box response element interactions. Biochem. J. 422:353-611
67. Levonen AL, Landar A, Ramachandran A, Ceaser EK, Dickinson DA, et al. 2004. Cellular mechanisms of redox cell signalling: role of cysteine modification in controlling antioxidant defences in response to electrophilic lipid oxidation products. Biochem. J. 378:373-822
68. Oh JY, Giles N, Landar A, Darley-Usmar V. 2008. Accumulation of 15-deoxy-12,14-prostaglandin J2 adduct formation with Keap1 over time: effects on potency for intracellular antioxidant defence induction. Biochem. J. 411:297-3066
69. Hosoya T, Maruyama A, Kang MI,KawataniY, Shibata T, et al. 2005. Differential responses of the Nrf2-Keap1 system to laminar and oscillatory shear stresses in endothelial cells. J. Biol. Chem. 280:27244-500
70. Itoh K, Mochizuki M, Ishii Y, Ishii T, Shibata T, et al. 2004. Transcription factor Nrf2 regulates inflammation by mediating the effect of 15-deoxy-12,14-prostaglandin J2. Mol. Cell. Biol. 24:36-455
71. Chaves SS, Groeger J, Helgenberger L, Auerbach SB, Bialek SR, et al. 2010. Improved anamnestic response among adolescents boosted with a higher dose of the hepatitis B vaccine. Vaccine 28:2860-644
72. Wang R, Kern JT, Goodfriend TL, Ball DL, Luesch H. 2009. Activation of the antioxidant response element by specific oxidized metabolites of linoleic acid. Prostaglandins Leukot. Essent. Fatty Acids 81:53-599
73. Wung BS, Wu CC, Hsu MC, Hsieh CW. 2006. 15-Deoxy-12,14-prostaglandin J2 suppresses IL-6-induced STAT3 phosphorylation via electrophilic reactivity in endothelial cells. Life Sci. 78:3035-422
74. JyrkkanenHK, Kuosmanen S,HeinaniemiM, Laitinen H, Kansanen E, et al. 2011. Novel insights into the regulation of antioxidant-response-element- mediated gene expression by electrophiles: induction of the transcriptional repressor BACH1 by Nrf2. Biochem. J. 440:167-744
75. Afonyushkin T, Oskolkova OV, Philippova M, Resink TJ, Erne P, et al. 2010. Oxidized phospholipids regulate expression of ATF4 and VEGF in endothelial cells via NRF2-dependent mechanism: novel point of convergence between electrophilic and unfolded protein stress pathways. Arterioscler. Thromb. Vasc. Biol. 30:1007-133
76. Tak PP, Firestein GS. 2001. NF-B: a key role in inflammatory diseases. J. Clin. Investig. 107:7-111
77. Cui T, Schopfer FJ, Zhang J, Chen K, Ichikawa T, et al. 2006. Nitrated fatty acids: endogenous anti-inflammatory signaling mediators. J. Biol. Chem. 281:35686-988
78. Villacorta L, Chang L, Salvatore SR, Ichikawa T, Zhang J, et al. 2012. Electrophilic nitro-fatty acids inhibit vascular inflammation by disrupting LPS-dependent TLR4 signalling in lipid rafts. Cardiovasc. Res. 98:116-244
79. Lin YC, Huang GD, Hsieh CW, Wung BS. 2012. The glutathionylation of p65 modulates NF-B activity in 15-deoxy-12,14-prostaglandin J2-treated endothelial cells. Free Radic. Biol. Med. 52:1844-533
80. Rovin BH, Lu L, Cosio A. 2001. Cyclopentenone prostaglandins inhibit cytokine-induced NF-B activation and chemokine production by human mesangial cells. J. Am. Soc. Nephrol. 12:1659-677
81. Castrillo A, Diaz-Guerra MJ, Hortelano S,Martin-Sanz P, Bosca L. 2000. Inhibition of IB kinase and IB phosphorylation by 15-deoxy-12,14-prostaglandin J2 in activated murine macrophages. Mol. Cell. Biol. 20:1692-988
82. Musiek ES, Brooks JD, Joo M, Brunoldi E, Porta A, et al. 2008. Electrophilic cyclopentenone neuroprostanes are anti-inflammatory mediators formed from the peroxidation of the omega-3 polyunsaturated fatty acid docosahexaenoic acid. J. Biol. Chem. 283:19927-355
83. Rossi A, Kapahi P, Natoli G, Takahashi T, Chen Y, et al. 2000. Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IB kinase. Nature 403:103-88
84. Tontonoz P, Spiegelman BM. 2008. Fat and beyond: the diverse biology of PPAR?. Annu. Rev. Biochem. 77:289-3122
85. Li Y, Zhang J, Schopfer FJ, Martynowski D, Garcia-Barrio MT, et al. 2008. Molecular recognition of nitrated fatty acids by PPAR?. Nat. Struct. Mol. Biol. 15:865-677
86. Waku T, Shiraki T, Oyama T, Fujimoto Y, Maebara K, et al. 2009. Structural insight into PPAR activation through covalent modification with endogenous fatty acids. J. Mol. Biol. 385:188-999
87. Schopfer FJ, Lin Y, Baker PR, Cui T, Garcia-Barrio M, et al. 2005. Nitrolinoleic acid: an endogenous peroxisome proliferator-activated receptor ligand. Proc. Natl. Acad. Sci. USA 102:2340-455
88. Baker PR, Lin Y, Schopfer FJ,Woodcock SR, Groeger AL, et al. 2005. Fatty acid transduction of nitric oxide signaling: Multiple nitrated unsaturated fatty acid derivatives exist in human blood and urine and serve as endogenous peroxisome proliferator-activated receptor ligands. J. Biol. Chem. 280:42464-755
89. BakerPR, Schopfer FJ, Sweeney S, Freeman BA. 2004. Red cellmembrane and plasma linoleic acid nitration products: synthesis, clinical identification, and quantitation. Proc.Natl. Acad. Sci.USA101:11577-822
90. Rudolph V, Rudolph TK, Schopfer FJ, Bonacci G, Woodcock SR, et al. 2010. Endogenous generation and protective effects of nitro-fatty acids in a murine model of focal cardiac ischaemia and reperfusion. Cardiovasc. Res. 85:155-666
91. Zhang J, Villacorta L, Chang L, Fan Z, Hamblin M, et al. 2010. Nitro-oleic acid inhibits angiotensin II-induced hypertension. Circ. Res. 107:540-488
92. Kliewer SA, Lenhard JM, Willson TM, Patel I, Morris DC, Lehmann JM. 1995. A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor and promotes adipocyte differentiation. Cell 83:813-199
93. Itoh T, Fairall L, Amin K, Inaba Y, Szanto A, et al. 2008. Structural basis for the activation of PPAR by oxidized fatty acids. Nat. Struct. Mol. Biol. 15:924-311
94. Alexander RL, Bates DJ, Wright MW, King SB, Morrow CS. 2006. Modulation of nitrated lipid signaling by multidrug resistance protein 1 (MRP1): Glutathione conjugation andMRP1-mediated efflux inhibit nitrolinoleic acid-induced, PPAR-dependent transcription activation. Biochemistry 45:7889-966
95. Straus DS, Glass CK. 2001. Cyclopentenone prostaglandins: new insights on biological activities and cellular targets. Med. Res. Rev. 21:185-2100
96. Rawlings JS, Rosler KM, Harrison DA. 2004. The JAK/STAT signaling pathway. J. Cell Sci. 117:1281-833
97. Ichikawa T, Zhang J,ChenK, Liu Y, Schopfer FJ, et al. 2008. Nitroalkenes suppress lipopolysaccharideinduced signal transducer and activator of transcription signaling in macrophages: a critical role of mitogen-activated protein kinase phosphatase 1. Endocrinology 149:4086-944
98. Venema RC, Venema VJ, Eaton DC, Marrero MB. 1998. Angiotensin II-induced tyrosine phosphorylation of signal transducers and activators of transcription 1 is regulated by Janus-activated kinase 2 and Fyn kinases and mitogen-activated protein kinase phosphatase 1. J. Biol. Chem. 273:30795-8000
99. Park EJ, Park SY, Joe EH, Jou I. 2003. 15d-PGJ2 and rosiglitazone suppress Janus kinase-STAT inflammatory signaling through induction of suppressor of cytokine signaling 1 (SOCS1) and SOCS3 in glia. J. Biol. Chem. 278:14747-522
100. Trostchansky A, Souza JM, Ferreira A, Ferrari M, Blanco F, et al. 2007. Synthesis, isomer characterization, and anti-inflammatory properties of nitroarachidonate. Biochemistry 46:4645-533
101. Salvemini D, Kim SF, Mollace V. 2013. Reciprocal regulation of the nitric oxide and cyclooxygenase pathway in pathophysiology: relevance and clinical implications. Am. J. Physiol. Regul. Integr. Comp. Physiol. 304:R473-877
102. Khoo NK, Rudolph V, Cole MP, Golin-Bisello F, Schopfer FJ, et al. 2010. Activation of vascular endothelial nitric oxide synthase and heme oxygenase-1 expression by electrophilic nitro-fatty acids. Free Radic. Biol. Med. 48:230-399
103. Trostchansky A, Bonilla L, Thomas CP, O'Donnell VB, Marnett LJ, et al. 2011. Nitroarachidonic acid, a novel peroxidase inhibitor of prostaglandin endoperoxide H synthases 1 and 2. J. Biol. Chem. 286:12891-9000
104. Chakraborti AK, Garg SK, Kumar R,Motiwala HF, Jadhavar PS. 2010. Progress in COX-2 inhibitors: a journey so far. Curr. Med. Chem. 17:1563-933
105. Newby AC. 2007. Metalloproteinases and vulnerable atherosclerotic plaques. Trends Cardiovasc. Med. 17:253-588
106. Parks WC, Wilson CL, Lopez-Boado YS. 2004. Matrix metalloproteinases as modulators of inflammation and innate immunity. Nat. Rev. Immunol. 4:617-299
107. Bonacci G, Schopfer FJ, Batthyany CI, Rudolph TK, Rudolph V, et al. 2011. Electrophilic fatty acids regulate matrix metalloproteinase activity and expression. J. Biol. Chem. 286:16074-811
108. Kelley EE, Batthyany CI, Hundley NJ,Woodcock SR, Bonacci G, et al. 2008. Nitro-oleic acid, a novel and irreversible inhibitor of xanthine oxidoreductase. J. Biol. Chem. 283:36176-844
109. Alvarez-Maqueda M, El Bekay R, Alba G, Monteseirin J, Chacon P, et al. 2004. 15-Deoxy-12,14-prostaglandin J2 induces heme oxygenase-1 gene expression in a reactive oxygen species-dependent manner in human lymphocytes. J. Biol. Chem. 279:21929-377
110. Harris SG, Smith RS, Phipps RP. 2002. 15-Deoxy-12,14-PGJ2 induces IL-8 production in human T cells by a mitogen-activated protein kinase pathway. J. Immunol. 168:1372-799
111. Meade EA, McIntyre TM, Zimmerman GA, Prescott SM. 1999. Peroxisome proliferators enhance cyclooxygenase-2 expression in epithelial cells. J. Biol. Chem. 274:8328-344
112. Shibata T, Yamada T, Ishii T, Kumazawa S, Nakamura H, et al. 2003. Thioredoxin as a molecular target of cyclopentenone prostaglandins. J. Biol. Chem. 278:26046-544
113. Haskew-LaytonRE, Payappilly JB,XuH, Bennett SA,Ratan RR. 2013. 15-Deoxy-12,14-prostaglandin J2 (15d-PGJ2) protects neurons from oxidative death via an Nrf2 astrocyte-specific mechanism independent of PPAR?. J. Neurochem. 124:536-477
114. LoPachin RM, Barber DS, Gavin T. 2008. Molecular mechanisms of the conjugated, β-unsaturated carbonyl derivatives: relevance to neurotoxicity and neurodegenerative diseases. Toxicol. Sci. 104:235-499
115. Kumagai T,Matsukawa N, Kaneko Y, Kusumi Y, MitsumataM, Uchida K. 2004. A lipid peroxidation-derived inflammatory mediator: identification of 4-hydroxy-2-nonenal as a potential inducer of cyclooxygenase-2 in macrophages. J. Biol. Chem. 279:48389-966
116. Motter AL, Ahern GP. 2012. TRPA1 is a polyunsaturated fatty acid sensor in mammals. PLoS ONE 7:e384399
117. Sculptoreanu A, Kullmann FA, Artim DE, Bazley FA, Schopfer F, et al. 2010. Nitro-oleic acid inhibits firing and activates TRPV1-and TRPA1-mediated inward currents in dorsal root ganglion neurons from adult male rats. J. Pharmacol. Exp. Ther. 333:883-955
118. Artim DE, Bazely F, Daugherty SL, Sculptoreanu A, Koronowski KB, et al. 2011. Nitro-oleic acid targets transient receptor potential (TRP) channels in capsaicin sensitive afferent nerves of rat urinary bladder. Exp. Neurol. 232:90-999
119. Macpherson LJ, Dubin AE, Evans MJ, Marr F, Schultz PG, et al. 2007. Noxious compounds activate TRPA1 ion channels through covalent modification of cysteines. Nature 445:541-455
120. Taylor-Clark TE, Ghatta S, Bettner W, Undem BJ. 2009. Nitrooleic acid, an endogenous product of nitrative stress, activates nociceptive sensory nerves via the direct activation of TRPA1. Mol. Pharmacol. 75:820-299
121. Woodcock J, Sharfstein JM, Hamburg M. 2010. Regulatory action on rosiglitazone by the US Food and Drug Administration. N. Engl. J. Med. 363:1489-911
122. Yamamoto K, Itoh T, Abe D, Shimizu M, Kanda T, et al. 2005. Identification of putative metabolites of docosahexaenoic acid as potent PPAR agonists and antidiabetic agents. Bioorg. Med. Chem. Lett. 15:517-222
123. Stirban A, Nandrean S, Gotting C, Tamler R, Pop A, et al. 2010. Effects of n-3 fatty acids on macroand microvascular function in subjects with type 2 diabetes mellitus. Am. J. Clin. Nutr. 91:808-133
124. Gonzalez-Periz A, Horrillo R, Ferre N, Gronert K, Dong B, et al. 2009. Obesity-induced insulin resistance and hepatic steatosis are alleviated by omega-3 fatty acids: a role for resolvins and protectins. FASEB J. 23:1946-577
125. Pace-Asciak CR, Mizuno K, Yamamoto S, Granstrom E, Samuelsson B. 1983. Oxygenation of arachidonic acid into 8,11,12-and 10,11,12- trihydroxyeicosatrienoic acid by rat lung. Adv. Prostaglandin Thromboxane Leukot. Res. 11:133-399
126. Wang H, Liu H, Jia Z, Guan G, Yang T. 2010. Effects of endogenous PPAR agonist nitro-oleic acid on metabolic syndrome in obese Zucker rats. PPAR Res. 2010:6015622
127. Liu S, Jia Z, Zhou L, Liu Y, Ling H, et al. 2013. Nitro-oleic acid protects against adriamycin-induced nephropathy in mice. Am. J. Physiol. Ren. Physiol. 305(11):F11533-411
128. Wang H, Liu H, Jia Z, Olsen C, Litwin S, et al. 2010. Nitro-oleic acid protects against endotoxininduced endotoxemia and multiorgan injury in mice. Am. J. Physiol. Ren. Physiol. 298:F754-622
129. Liu H, Jia Z, Soodvilai S, Guan G, Wang MH, et al. 2008. Nitro-oleic acid protects the mouse kidney from ischemia and reperfusion injury. Am. J. Physiol. Ren. Physiol. 295:F942-499
130. ZhuH, Zhang L, Amin AR, Li Y. 2008. Coordinated upregulation of a series of endogenous antioxidants and phase 2 enzymes as a novel strategy for protecting renal tubular cells from oxidative and electrophilic stress. Exp. Biol. Med. 233:753-655
131. Nadtochiy SM, Baker PR, Freeman BA, Brookes PS. 2009. Mitochondrial nitroalkene formation and mild uncoupling in ischaemic preconditioning: implications for cardioprotection. Cardiovasc. Res. 82:333-400
132. Nadtochiy SM, ZhuQ,UrciuoliW, Rafikov R, Black SM, Brookes PS. 2012. Nitroalkenes confer acute cardioprotection via adenine nucleotide translocase 1. J. Biol. Chem. 287:3573-800
133. Kim K, Jung N, Lee K, Choi J, Kim S, et al. 2013. Dietary omega-3 polyunsaturated fatty acids attenuate hepatic ischemia/reperfusion injury in rats by modulating Toll-like receptor recruitment into lipid rafts. Clin. Nutr. 32(5):855-622
134. Giaginis C, Tsantili-Kakoulidou A, Theocharis S. 2008. Peroxisome proliferator-activated receptor-ligands: potential pharmacological agents for targeting the angiogenesis signaling cascade in cancer. PPAR Res. 2008:4317633
135. Villacorta L, Chang L, Salvatore SR, Ichikawa T, Zhang J, et al. 2013. Electrophilic nitro-fatty acids inhibit vascular inflammation by disrupting LPS-dependent TLR4 signalling in lipid rafts. Cardiovasc. Res. 98:116-244
136. Coles B, Bloodsworth A, Eiserich JP, Coffey MJ, McLoughlin RM, et al. 2002. Nitrolinoleate inhibits platelet activation by attenuating calcium mobilization and inducing phosphorylation of vasodilatorstimulated phosphoprotein through elevation of cAMP. J. Biol. Chem. 277:5832-400
137. Coles B, Bloodsworth A, Clark SR, Lewis MJ, Cross AR, et al. 2002. Nitrolinoleate inhibits superoxide generation, degranulation, and integrin expression by human neutrophils: novel antiinflammatory properties of nitric oxide-derived reactive species in vascular cells. Circ. Res. 91:375-811
138. Della Bona R, Cardillo MT, Leo M, Biasillo G, Gustapane M, et al. 2013. Polymorphonuclear neutrophils and instability of the atherosclerotic plaque: a causative role? Inflamm. Res. 62:537-500
139. Rudolph TK, Rudolph V, Edreira MM, Cole MP, Bonacci G, et al. 2010. Nitro-fatty acids reduce atherosclerosis in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 30:938-455
140. Nadtochiy SM, Redman EK. 2011. Mediterranean diet and cardioprotection: the role of nitrite, polyunsaturated fatty acids, and polyphenols. Nutrition 27:733-444
141. Gross GJ, Hsu A, Falck JR, Nithipatikom K. 2007. Mechanisms by which epoxyeicosatrienoic acids (EETs) elicit cardioprotection in rat hearts. J. Mol. Cell. Cardiol. 42:687-911
142. Wayman NS, Hattori Y, McDonald MC, Mota-Filipe H, Cuzzocrea S, et al. 2002. Ligands of the peroxisome proliferator-activated receptors (PPAR-and PPAR-) reduce myocardial infarct size. FASEB J. 16:1027-400
143. Zingarelli B, Hake PW, Mangeshkar P, O'ConnorM, Burroughs TJ, et al. 2007. Diverse cardioprotective signaling mechanisms of peroxisome proliferator-activated receptor-ligands, 15-deoxy-12,14-prostaglandin J2 and ciglitazone, in reperfusion injury: role of nuclear factor-B, heat shock factor 1, and Akt. Shock 28:554-633
144. Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, et al. 2002. Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'InfartoMiocardico (GISSI)-Prevenzione. Circulation 105:1897-9033
145. Guo CJ, Schopfer FJ, Gonzales L, Wang P, Freeman BA, Gow AJ. 2011. Atypical PKC transduces electrophilic fatty acid signaling in pulmonary epithelial cells. Nitric Oxide 25:366-722
146. Reddy AT, Lakshmi SP, Reddy RC. 2012. The nitrated fatty acid 10-nitro-oleate diminishes severity of LPS-induced acute lung injury in mice. PPAR Res. 2012:617063
147. Schermuly RT, Stasch JP, Pullamsetti SS, Middendorff R, MullerD, et al. 2008. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur. Respir. J. 32:881-911
148. El Kebir D, Jozsef L, Pan W, Wang L, Petasis NA, et al. 2009. 15-Epi-lipoxin A4 inhibits myeloperoxidase signaling and enhances resolution of acute lung injury. Am. J. Respir. Crit. CareMed. 180:311-199
149. Karp CL, Flick LM, Park KW, Softic S, Greer TM, et al. 2004. Defective lipoxin-mediated antiinflammatory activity in the cystic fibrosis airway. Nat. Immunol. 5:388-922
150. Karp CL, Flick LM, Yang R, Uddin J, Petasis NA. 2005. Cystic fibrosis and lipoxins. Prostaglandins Leukot. Essen. Fatty Acids 73:263-700
151. Levy BD, De Sanctis GT, Devchand PR, Kim E, Ackerman K, et al. 2002. Multi-pronged inhibition of airway hyper-responsiveness and inflammation by lipoxin A4. Nat. Med. 8:1018-233
152. Levy BD, Kohli P, Gotlinger K, Haworth O, Hong S, et al. 2007. Protectin D1 is generated in asthma and dampens airway inflammation and hyperresponsiveness. J. Immunol. 178:496-5022
153. Farnesi-de-Assuncao TS, Alves CF, Carregaro V, de Oliveira JR, da Silva CA, et al. 2012. PPAR-agonists, mainly 15d-PGJ2, reduce eosinophil recruitment following allergen challenge. Cell. Immunol. 273:23-299
154. Mochizuki M, Ishii Y, Itoh K, Iizuka T, Morishima Y, et al. 2005. Role of 15-deoxy 12,14 prostaglandin J2 and Nrf2 pathways in protection against acute lung injury.Am. J. Respir. Crit.CareMed. 171:1260-666
155. Rangasamy T, Guo J, Mitzner WA, Roman J, Singh A, et al. 2005. Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice. J. Exp. Med. 202:47-599
156. Suzuki M, BetsuyakuT, Ito Y, Nagai K,Nasuhara Y, et al. 2008. Down-regulated NF-E2-related factor 2 in pulmonary macrophages of aged smokers and patients with chronic obstructive pulmonary disease. Am. J. Respir. Cell Mol. Biol. 39:673-822
157. Surh YJ, Na HK, Park JM, Lee HN, Kim W, et al. 2011. 15-Deoxy 12,14-prostaglandin J2, an electrophilic lipid mediator of anti-inflammatory and pro-resolving signaling. Biochem. Pharmacol. 82:1335-511
158. Borniquel S, Jansson EA, Cole MP, Freeman BA, Lundberg JO. 2010. Nitrated oleic acid up-regulates PPAR and attenuates experimental inflammatory bowel disease. Free Radic. Biol. Med. 48:499-5055
159. Knopfova L, Smarda J. 2010. The use of Cox-2 and PPAR signaling in anti-cancer therapies. Exp. Ther. Med. 1:257-644
160. Fritz KS, Petersen DR. 2013. An overview of the chemistry and biology of reactive aldehydes. Free Radic. Biol. Med. 59:85-911
161. Nishida M, Sawa T, KitajimaN, Ono K, Inoue H, et al. 2012. Hydrogen sulfide anion regulates redox signaling via electrophile sulfhydration. Nat. Chem. Biol. 8:714-244