1,736
Views
69
CrossRef citations to date
0
Altmetric
Review Article

Cytochrome P450 2J2: distribution, function, regulation, genetic polymorphisms and clinical significance

, , , &
Pages 311-352 | Received 27 Mar 2013, Accepted 14 May 2013, Published online: 19 Jul 2013

Reference

  • Aboutabl ME, Zordoky BN, El-Kadi AO. (2009). 3-Methylcholanthrene and benzo(a)pyrene modulate cardiac cytochrome P450 gene expression and arachidonic acid metabolism in male Sprague Dawley rats. Br J Pharmacol 158:1808–1819
  • Aiba I, Yamasaki T, Shinki T, et al. (2006). Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Steroids 71:849–856
  • Aida K, Negishi M. (1991). Posttranscriptional regulation of coumarin 7-hydroxylase induction by xenobiotics in mouse liver: mRNA stabilization by pyrazole. Biochemistry 30:8041–8045
  • Akhmadishina LA, Korytina GF, Victorova TV. (2011). [Polymorphic markers of the CYP1B1 (4326C > G), CYP2F1 (c.14_15insC), CYP2J2 (−76G > T), and CYP2S1 (13106C > T and 13255A > G) genes and genetic predisposition to chronic respiratory diseases induced by smoking and occupational factors]. Genetika 47:1402–1410
  • Alghasham A, Ali A, Ismail H, et al. (2012). CYP2J2 -50 G/T and ADRB2 G46A Gene Polymorphisms in Saudi Subjects with Hypertension. Genet Test Mol Biomarkers
  • Alsaad AM, Zordoky BN, El-Sherbeni AA, El-Kadi AO. (2012). Chronic doxorubicin cardiotoxicity modulates cardiac cytochrome P450-mediated arachidonic acid metabolism in rats. Drug Metab Dispos
  • Alvarez DF, Gjerde EA, Townsley MI. (2004). Role of EETs in regulation of endothelial permeability in rat lung. Am J Physiol – Lung Cell Mol Physiol 286:L445–L451
  • Angel P, Karin M. (1991). The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1072:129–157
  • Anwar-Mohamed A, Zordoky BN, Aboutabl ME, El-Kadi AO. (2010). Alteration of cardiac cytochrome P450-mediated arachidonic acid metabolism in response to lipopolysaccharide-induced acute systemic inflammation. Pharmacol Res 61:410–418
  • Armas LA, Hollis BW, Heaney RP. (2004). Vitamin D2 is much less effective than vitamin D3 in humans. J Clin Endocrinol Metabol 89:5387–5391
  • Arnold C, Markovic M, Blossey K, et al. (2010). Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of {omega}-3 fatty acids. J Biol Chem 285:32720–32733
  • Athirakul K, Bradbury JA, Graves JP, et al. (2008). Increased blood pressure in mice lacking cytochrome P450 2J5. FASEB J 22:4096–4108
  • Bandi N, Zbinden S, Gugger M, et al. (2009). miR-15a and miR-16 are implicated in cell cycle regulation in a Rb-dependent manner and are frequently deleted or down-regulated in non-small cell lung cancer. Cancer Res 69:5553–5559
  • Batchu SN, Law E, Brocks DR, et al. (2009). Epoxyeicosatrienoic acid prevents postischemic electrocardiogram abnormalities in an isolated heart model. J Mol Cell Cardiol 46:67–74
  • Behrens A, Sibilia M, Wagner EF. (1999). Amino-terminal phosphorylation of c-Jun regulates stress-induced apoptosis and cellular proliferation. Nat Genet 21:326–329
  • Bellien J, Joannides R, Richard V, Thuillez C. (2011). Modulation of cytochrome-derived epoxyeicosatrienoic acids pathway: A promising pharmacological approach to prevent endothelial dysfunction in cardiovascular diseases? Pharmacol Ther 131:1–17
  • Berlin DS, Sangkuhl K, Klein TE, Altman RB. (2011). PharmGKB summary: Cytochrome P450, family 2, subfamily J, polypeptide 2: CYP2J2. Pharmacogenet Genomics 21:308–311
  • Bieche I, Narjoz C, Asselah T, et al. (2007). Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues. Pharmacogenet Genomics 17:731–742
  • Borgel J, Bulut D, Hanefeld C, et al. (2008). The CYP2J2 G-50T polymorphism and myocardial infarction in patients with cardiovascular risk profile. BMC Cardiovasc Disord 8:41
  • Bylund J, Kunz T, Valmsen K, Oliw EH. (1998). Cytochromes P450 with bisallylic hydroxylation activity on arachidonic and linoleic acids studied with human recombinant enzymes and with human and rat liver microsomes. J Pharmacol Exp Ther 284:51–60
  • Bystrom J, Wray JA, Sugden MC, et al. (2011). Endogenous epoxygenases are modulators of monocyte/macrophage activity. PLoS One 6:e26591
  • Capdevila JH, Falck JR, Estabrook RW. (1992a). Cytochrome P450 and the arachidonate cascade. FASEB J 6:731–736
  • Capdevila JH, Falck JR, Imig JD. (2007). Roles of the cytochrome P450 arachidonic acid monooxygenases in the control of systemic blood pressure and experimental hypertension. Kidney Int 72:683–689
  • Capdevila JH, Wei S, Yan J, et al. (1992b). Cytochrome P-450 arachidonic acid epoxygenase. Regulatory control of the renal epoxygenase by dietary salt loading. J Biol Chem 267:21720–21726
  • Carroll MA, Balazy M, Margiotta P, et al. (1993). Renal vasodilator activity of 5,6-epoxyeicosatrienoic acid depends upon conversion by cyclooxygenase and release of prostaglandins. J Biol Chem 268:12260–12266
  • Carroll MA, Garcia MP, Falck JR, McGiff JC. (1992). Cyclooxygenase dependency of the renovascular actions of cytochrome P450-derived arachidonate metabolites. J Pharmacol Exp Ther 260:104–109
  • Catella F, Lawson JA, Fitzgerald DJ, FitzGerald GA. (1990). Endogenous biosynthesis of arachidonic acid epoxides in humans: Increased formation in pregnancy-induced hypertension. Proc Natl Acad Sci U S A 87:5893–5897
  • Chackalamannil S, Wang Y, Greenlee WJ, et al. (2008). Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activity. J Med Chem 51:3061–3064
  • Chen C, Li G, Liao W, et al. (2009). Selective inhibitors of CYP2J2 related to terfenadine exhibit strong activity against human cancers in vitro and in vivo. J Pharmacol Exp Ther 329:908–918
  • Chen C, Wei X, Rao X, et al. (2011a). Cytochrome P450 2J2 is highly expressed in hematologic malignant diseases and promotes tumor cell growth. J Pharmacol Exp Ther 336:344–355
  • Chen CZ, Li L, Lodish HF, Bartel DP. (2004). MicroRNAs modulate hematopoietic lineage differentiation. Science 303:83–86
  • Chen F, Chen C, Yang S, et al. (2012). Let-7b inhibits human cancer phenotype by targeting cytochrome P450 epoxygenase 2J2. PLoS One 7:e39197
  • Chen G, Wang P, Zhao G, et al. (2011b). Cytochrome P450 epoxygenase CYP2J2 attenuates nephropathy in streptozotocin-induced diabetic mice. Prostaglandins Other Lipid Mediat 96:63–71
  • Chen K, Rajewsky N. (2007). The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet 8:93–103
  • Cheng AM, Byrom MW, Shelton J, Ford LP. (2005). Antisense inhibition of human miRNAs and indications for an involvement of miRNA in cell growth and apoptosis. Nucleic Acids Res 33:1290–1297
  • Cheng JB, Motola DL, Mangelsdorf DJ, Russell DW. (2003). De-orphanization of Cytochrome P450 2R1 a microsomal vitamin D 25-hydroxylase. J Biol Chem 278:38084–38093
  • Corton JC, Fan LQ, Brown S, et al. (1998). Down-regulation of cytochrome P450 2C family members and positive acute-phase response gene expression by peroxisome proliferator chemicals. Mol Pharmacol 54:463–473
  • Conroy JL, Nalwalk JW, Phillips JG, Hough LB. (2013). CC12, a P450/Epoxygenase inhibitor, acts in the rat rostral, ventromedial medulla to attenuate morphine antinociception. Brain Res
  • Cowart LA, Wei S, Hsu MH, et al. (2002). The CYP4A isoforms hydroxylate epoxyeicosatrienoic acids to form high affinity peroxisome proliferator-activated receptor ligands. J Biol Chem 277:35105–35112
  • Delozier TC, Kissling GE, Coulter SJ, et al. (2007). Detection of human CYP2C8, CYP2C9, and CYP2J2 in cardiovascular tissues. Drug Metab Dispos 35:682–688
  • DeLuca HF. (2004). Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr 80:1689S–1696S
  • Deng P, You T, Chen X, et al. (2011a). Identification of amiodarone metabolites in human bile by ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry. Drug Metab Dispos 39:1058–1069
  • Deng Y, Edin ML, Theken KN, et al. (2011b). Endothelial CYP epoxygenase overexpression and soluble epoxide hydrolase disruption attenuate acute vascular inflammatory responses in mice. FASEB J 25:703–713
  • Derhaschnig U, Schweeger-Exeli I, Marsik C, et al. (2010). Effects of aspirin and NO-aspirin (NCX 4016) on platelet function and coagulation in human endotoxemia. Platelets 21:320–328
  • Ding X, Kaminsky LS. (2003). Human extrahepatic cytochromes P450: Function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annu Rev Pharmacol Toxicol 43:149–173
  • Draper AJ, Hammock BD. (2000). Identification of CYP2C9 as a human liver microsomal linoleic acid epoxygenase. Arch Biochem Biophys 376:199–205
  • Dreisbach AW, Japa S, Sigel A, et al. (2005). The Prevalence of CYP2C8, 2C9, 2J2, and soluble epoxide hydrolase polymorphisms in African Americans with hypertension. Am J Hypertens 18:1276–1281
  • Du L, Neis MM, Ladd PA, et al. (2006). Effects of the differentiated keratinocyte phenotype on expression levels of CYP1-4 family genes in human skin cells. Toxicol Appl Pharmacol 213:135–144
  • Dumoulin M, Salvail D, Gaudreault SB, et al. (1998). Epoxyeicosatrienoic acids relax airway smooth muscles and directly activate reconstituted KCa channels. Am J Physiol 275:L423–L431
  • Dutheil F, Dauchy S, Diry M, et al. (2009). Xenobiotic-metabolizing enzymes and transporters in the normal human brain: Regional and cellular mapping as a basis for putative roles in cerebral function. Drug Metab Dispos 37:1528–1538
  • Edin ML, Wang Z, Bradbury JA, et al. (2011). Endothelial expression of human cytochrome P450 epoxygenase CYP2C8 increases susceptibility to ischemia-reperfusion injury in isolated mouse heart. FASEB J 25:3436–3447
  • Elbekai RH, El-Kadi AO. (2006). Cytochrome P450 enzymes: Central players in cardiovascular health and disease. Pharmacol Ther 112:564–587
  • Enayetallah AE, French RA, Thibodeau MS, Grant DF. (2004). Distribution of soluble epoxide hydrolase and of cytochrome P450 2C8, 2C9, and 2J2 in human tissues. J Histochem Cytochem 52:447–454
  • Esquela-Kerscher A, Slack FJ. (2006). Oncomirs – MicroRNAs with a role in cancer. Nat Rev Cancer 6:259–269
  • Fabre G, Julian B, Saint-Aubert B, et al. (1993). Evidence for CYP3A-mediated N-deethylation of amiodarone in human liver microsomal fractions. Drug Metab Dispos 21:978–985
  • Falck JR, Manna S, Moltz J, et al. (1983). Epoxyeicosatrienoic acids stimulate glucagon and insulin release from isolated rat pancreatic islets. Biochem Biophys Res Commun 114:743–749
  • Fang X, Hu S, Xu B, et al. (2006). 14,15-Dihydroxyeicosatrienoic acid activates peroxisome proliferator-activated receptor-alpha. Am J Physiol Heart Circ Physiol 290:H55–H63
  • Fava C, Montagnana M, Almgren P, et al. (2010). The common functional polymorphism -50G > T of the CYP2J2 gene is not associated with ischemic coronary and cerebrovascular events in an urban-based sample of Swedes. J Hypertens 28:294–299
  • Fava C, Ricci M, Melander O, Minuz P. (2011). Hypertension, cardiovascular risk and polymorphisms in genes controlling the cytochrome P450 pathway of arachidonic acid: A sex-specific relation? Prostaglandins Other Lipid Mediat
  • Fer M, Dreano Y, Lucas D, et al. (2008). Metabolism of eicosapentaenoic and docosahexaenoic acids by recombinant human cytochromes P450. Arch Biochem Biophys 471:116–125
  • Fichtlscherer S, Dimmeler S, Breuer S, et al. (2004). Inhibition of cytochrome P4502C9 improves endothelium-dependent, nitric oxide-mediated vasodilatation in patients with coronary artery disease. Circulation 109:178–183
  • Fleming I, Michaelis UR, Bredenkotter D, et al. (2001). Endothelium-derived hyperpolarizing factor synthase (Cytochrome P450 2C9) is a functionally significant source of reactive oxygen species in coronary arteries. Circ Res 88:44–51
  • Freedman RS, Wang E, Voiculescu S, et al. (2007). Comparative analysis of peritoneum and tumor eicosanoids and pathways in advanced ovarian cancer. Clin Cancer Res 13:5736–5744
  • Friedman JM, Liang G, Liu CC, et al. (2009). The putative tumor suppressor microRNA-101 modulates the cancer epigenome by repressing the polycomb group protein EZH2. Cancer Res 69:2623–2629
  • Fulton D, Balazy M, McGiff JC, Quilley J. (1996). Possible contribution of platelet cyclooxygenase to the renal vascular action of 5,6-epoxyeicosatrienoic acid. J Pharmacol Exp Ther 277:1195–1199
  • Furukawa M, Nishimura M, Ogino D, et al. (2004). Cytochrome p450 gene expression levels in peripheral blood mononuclear cells in comparison with the liver. Cancer Sci 95:520–529
  • Gaedigk A, Baker DW, Totah RA, et al. (2006). Variability of CYP2J2 expression in human fetal tissues. J Pharmacol Exp Ther 319:523–532
  • Gervasini G, Vizcaino S, Carrillo JA, et al. (2006). The effect of CYP2J2, CYP3A4, CYP3A5 and the MDR1 polymorphisms and gender on the urinary excretion of the metabolites of the H-receptor antihistamine ebastine: A pilot study. Br J Clin Pharmacol 62:177–186
  • Ghosal A, Lu X, Penner N, et al. (2011). Identification of human liver cytochrome P450 enzymes involved in the metabolism of SCH 530348 (Vorapaxar), a potent oral thrombin protease-activated receptor 1 antagonist. Drug Metab Dispos 39:30–38
  • Godlewski J, Nowicki MO, Bronisz A, et al. (2008). Targeting of the Bmi-1 oncogene/stem cell renewal factor by microRNA-128 inhibits glioma proliferation and self-renewal. Cancer Res 68:9125–9130
  • Graves JP, Edin ML, Bradbury JA, et al. (2013). Characterization of Four New Mouse Cytochrome P450 Enzymes of the CYP2J Subfamily. Drug Metab Dispos
  • Gresele P, Migliacci R, Procacci A, et al. (2007). Prevention by NCX 4016, a nitric oxide-donating aspirin, but not by aspirin, of the acute endothelial dysfunction induced by exercise in patients with intermittent claudication. Thromb Haemost 97:444–450
  • Gresele P, Momi S. (2006). Pharmacologic profile and therapeutic potential of NCX 4016, a nitric oxide-releasing aspirin, for cardiovascular disorders. Cardiovasc Drug Rev 24:148–168
  • Gross GJ, Falck JR, Gross ER, et al. (2005). Cytochrome P450 and arachidonic acid metabolites: Role in myocardial ischemia/reperfusion injury revisited. Cardiovasc Res 68:18–25
  • Guengerich F. (1991). Reactions and significance of cytochrome P-450 enzymes. J Biol Chem 266
  • Ha HR, Bigler L, Binder M, et al. (2001). Metabolism of amiodarone (part I): Identification of a new hydroxylated metabolite of amiodarone. Drug Metab Dispos 29:152–158
  • Ha HR, Bigler L, Wendt B, et al. (2005). Identification and quantitation of novel metabolites of amiodarone in plasma of treated patients. Eur J Pharm Sci 24:271–279
  • Hashizume T, Imaoka S, Mise M, et al. (2002). Involvement of CYP2J2 and CYP4F12 in the metabolism of ebastine in human intestinal microsomes. J Pharmacol Exp Ther 300:298–304
  • Hashizume T, Mise M, Matsumoto S, et al. (2001). A novel cytochrome P450 enzyme responsible for the metabolism of ebastine in monkey small intestine. Drug Metab Dispos 29:798–805
  • Hashizume T, Mise M, Terauchi Y, et al. (1998). N-Dealkylation and hydroxylation of ebastine by human liver cytochrome P450. Drug Metab Dispos 26:566–571
  • He B, Liu L, Cook GA, et al. (2005). Tetraspanin CD82 attenuates cellular morphogenesis through down-regulating integrin alpha6-mediated cell adhesion. J Biol Chem 280:3346–3354
  • Healy E, Dempsey M, Lally C, Ryan MP. (1998). Apoptosis and necrosis: Mechanisms of cell death induced by cyclosporine A in a renal proximal tubular cell line. Kidney Int 54:1955–1966
  • Heinricher MM, Maire JJ, Lee D, et al. (2010). Physiological basis for inhibition of morphine and improgan antinociception by CC12, a P450 epoxygenase inhibitor. J Neurophysiol 104:3222–3230
  • Hermann M, Hellermann JP, Quitzau K, et al. (2009). CYP4A11 polymorphism correlates with coronary endothelial dysfunction in patients with coronary artery disease – The ENCORE Trials. Atherosclerosis 207:476–479
  • Herse F, Lamarca B, Hubel CA, et al. (2012). Cytochrome P450 subfamily 2J polypeptide 2 expression and circulating epoxyeicosatrienoic metabolites in preeclampsia. Circulation 126:2990–2999
  • Hess J, Angel P, Schorpp-Kistner M. (2004). AP-1 subunits: Quarrel and harmony among siblings. J Cell Sci 117:5965–5973
  • Heykants J, Van Peer A, Woestenborghs R, et al. (1986). Dose-proportionality, bioavailability, and steady-state kinetics of astemizole in man. Drug Dev Res 8:71–78
  • Hoffmann MM, Bugert P, Seelhorst U, et al. (2007). The -50G > T polymorphism in the promoter of the CYP2J2 gene in coronary heart disease: The Ludwigshafen Risk and Cardiovascular Health study. Clin Chem 53:539–540
  • Holtzman MJ. (1991). Arachidonic acid metabolism. Implications of biological chemistry for lung function and disease. Am Rev Respir Dis 143:188–203
  • Homma S, Koido S, Sagawa Y, et al. (2009). Antigenic stimulation with cytochrome P450 2J expressed in mouse hepatocellular carcinoma cells regulates host anti-tumour immunity. Clin Exp Immunol 156:344–352
  • Huang H, Chang HH, Xu Y, et al. (2006). Epoxyeicosatrienoic acid inhibition alters renal hemodynamics during pregnancy. Exp Biol Med (Maywood) 231:1744–1752
  • Huang S, Gibson GG. (1991). Differential induction of cytochromes P450 and cytochrome P450-dependent arachidonic acid metabolism by 3,4,5,3',4'-pentachlorobiphenyl in the rat and the guinea pig. Toxicol Appl Pharmacol 108:86–95
  • Hukkanen J, Pelkonen O, Hakkola J, Raunio H. (2002). Expression and regulation of xenobiotic-metabolizing cytochrome P450 (CYP) enzymes in human lung. Crit Rev Toxicol 32:391–411
  • Ichihara K, Kusunose E, Kaku M, et al. (1985). Separation of two constitutive forms of cytochrome P-450 active in aminopyrine N-demethylation from rabbit intestinal mucosa microsomes. Biochim Biophys Acta 831:99–105
  • Imamura Y, Shimizu K, Yamashita F, et al. (2001). Transport characteristics of ebastine and its metabolites across human intestinal epithelial Caco-2 cell monolayers. Biol Pharm Bull 24:930–934
  • Imig JD. (1999). Epoxyeicosatrienoic acids. Biosynthesis, regulation, and actions. Methods Mol Biol 120:173–192
  • Imig JD. (2000a). Eicosanoid regulation of the renal vasculature. Am J Physiol Renal Physiol 279:F965–981
  • Imig JD. (2000b). Epoxygenase metabolites. Epithelial and vascular actions. Mol Biotechnol 16:233–251
  • Imig JD, Navar LG, Roman RJ, et al. (1996). Actions of epoxygenase metabolites on the preglomerular vasculature. J Am Soc Nephrol 7:2364–2370
  • Imig JD, Zhao X, Zaharis CZ, et al. (2005). An orally active epoxide hydrolase inhibitor lowers blood pressure and provides renal protection in salt-sensitive hypertension. Hypertension 46:975–981
  • Ingelman-Sundberg M. (2004). Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): Clinical consequences, evolutionary aspects and functional diversity. Pharmacogen J 5:6–13
  • Irusta G, Murphy MJ, Perez WD, Hennebold JD. (2007). Dynamic expression of epoxyeicosatrienoic acid synthesizing and metabolizing enzymes in the primate corpus luteum. Mol Hum Reprod 13:541–548
  • Ishizuka T, Cheng J, Singh H, et al. (2008). 20-Hydroxyeicosatetraenoic acid stimulates nuclear factor-kappaB activation and the production of inflammatory cytokines in human endothelial cells. J Pharmacol Exp Ther 324:103–110
  • Jacobs ER, Zeldin DC. (2001). The lung HETEs (and EETs) up. Am J Physiol Heart Circ Physiol 280:H1–H10
  • Jiang JG, Chen CL, Card JW, et al. (2005). Cytochrome P450 2J2 promotes the neoplastic phenotype of carcinoma cells and is up-regulated in human tumors. Cancer Res 65:4707–4715
  • Jiang JG, Fu XN, Chen CL, Wang DW. (2009a). Expression of cytochrome P450 arachidonic acid epoxygenase 2J2 in human tumor tissues and cell lines. Ai Zheng 28:93–96
  • Jiang JG, Ning YG, Chen C, et al. (2007). Cytochrome p450 epoxygenase promotes human cancer metastasis. Cancer Res 67:6665–6674
  • Jiang JG, Shen GF, Chen C, et al. (2009b). Effects of cytochrome P450 arachidonic acid epoxygenases on the proliferation of tumor cells. Ai Zheng 28:14–19
  • Jie Z, Hong K, Jianhong T, et al. (2010). Haplotype analysis of the CYP2J2 gene associated with myocardial infarction in a Chinese Han population. Cell Biochem Funct 28:435–439
  • Johnson EF, Stout CD. (2005). Structural diversity of human xenobiotic-metabolizing cytochrome P450 monooxygenases. Biochem Biophys Res Commun 338:331–336
  • Jones BC, Hyland R, Ackland M, et al. (1998). Interaction of terfenadine and its primary metabolites with cytochrome P450 2D6. Drug Metab Dispos 26:875–882
  • Kaminsky LS, Fasco MJ. (1992). Small intestinal cytochromes P450. CRC Crit Rev Toxicol 21:407–422
  • Kannan R, Miller S, Singh BN. (1985). Tissue uptake and metabolism of amiodarone after chronic administration in rabbits. Drug Metab Dispos 13:646–650
  • Karara A, Dishman E, Jacobson H, et al. (1990). Arachidonic acid epoxygenase: Stereochemical analysis of the endogenous epoxyeicosatrienoic acids of human kidney cortex. FEBS Lett 268:227–230
  • Karch S, Billingham M. (1988). The pathology and etiology of cocaine-induced heart disease. Archives of pathology & laboratory medicine 112:225
  • Keserü, B., Barbosa-Sicard E, Popp R, et al. (2008). Epoxyeicosatrienoic acids and the soluble epoxide hydrolase are determinants of pulmonary artery pressure and the acute hypoxic pulmonary vasoconstrictor response. FASEB J 22:4306–4315
  • Kikuta Y, Sogawa K, Haniu M, et al. (1991). A novel species of cytochrome P-450 (P-450ib) specific for the small intestine of rabbits. cDNA cloning and its expression in COS cells. J Biol Chem 266:17821–17825
  • King LM, Gainer JV, David GL, et al. (2005). Single nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension. Pharmacogenet Genomics 15:7–13
  • King LM, Ma J, Srettabunjong S, et al. (2002). Cloning of CYP2J2 gene and identification of functional polymorphisms. Mol Pharmacol 61:840–852
  • Kloosterman WP, Plasterk RH. (2006). The diverse functions of microRNAs in animal development and disease. Dev Cell 11:441–450
  • Koike K, Kusunose E, Nishikawa Y, et al. (1997). Purification and characterization of rabbit small intestinal cytochromes P450 belonging to CYP2J and CYP4A subfamilies. Biochem Biophys Res Commun 232:643–647
  • Konkel A, Schunck WH. (2011). Role of cytochrome P450 enzymes in the bioactivation of polyunsaturated fatty acids. Biochim Biophys Acta 1814:210–222
  • Kovacic-Milivojevic B, Gardner DG. (1992). Divergent regulation of the human atrial natriuretic peptide gene by c-jun and c-fos. Mol Cell Biol 12:292–301
  • Kris-Etherton PM, Harris WS, Appel LJ. (2002). Fish consumption, fish oil, omega-3 fatty acids, and cardiovascular disease. Circulation 106:2747–2757
  • Kroetz DL, Zeldin DC. (2002). Cytochrome P450 pathways of arachidonic acid metabolism. Curr Opin Lipidol 13:273–283
  • Kuehl P, Zhang J, Lin Y, et al. (2001). Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 27:383–391
  • Lafite P, Andre F, Zeldin DC, et al. (2007a). Unusual regioselectivity and active site topology of human cytochrome P450 2J2. Biochemistry 46:10237–10247
  • Lafite P, Dijols S, Buisson D, et al. (2006). Design and synthesis of selective, high-affinity inhibitors of human cytochrome P450 2J2. Bioorg Med Chem Lett 16:2777–2780
  • Lafite P, Dijols S, Zeldin DC, et al. (2007b). Selective, competitive and mechanism-based inhibitors of human cytochrome P450 2J2. Arch Biochem Biophys 464:155–168
  • Lafyatis R, Kim SJ, Angel P, et al. (1990). Interleukin-1 stimulates and all-trans-retinoic acid inhibits collagenase gene expression through its 5' activator protein-1-binding site. Mol Endocrinol 4:973–980
  • Lee AC, Murray M. (2010). Up-regulation of human CYP2J2 in HepG2 cells by butylated hydroxyanisole is mediated by c-Jun and Nrf2. Mol Pharmacol 77:987–994
  • Lee CA, Jones JP, 3rd, Katayama J, et al. (2012). Identifying a selective substrate and inhibitor pair for the evaluation of CYP2J2 activity. Drug Metab Dispos 40:943–951
  • Lee CA, Neul D, Clouser-Roche A, et al. (2010a). Identification of novel substrates for human cytochrome P450 2J2. Drug Metab Dispos 38:347–356
  • Lee CR, Imig JD, Edin ML, et al. (2010b). Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice. FASEB J 24:3770–3781
  • Lee CR, North KE, Bray MS, et al. (2007). CYP2J2 and CYP2C8 polymorphisms and coronary heart disease risk: The Atherosclerosis Risk in Communities (ARIC) study. Pharmacogenet Genomics 17:349–358
  • Lee RC, Feinbaum RL, Ambros V. (1993). The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854
  • Lee SS, Jeong HE, Liu KH, et al. (2005). Identification and functional characterization of novel CYP2J2 variants: G312R variant causes loss of enzyme catalytic activity. Pharmacogenet Genomics 15:105–113
  • Li R, Xu X, Chen C, et al. (2012). Cytochrome P450 2J2 is protective against global cerebral ischemia in transgenic mice. Prostaglandins Other Lipid Mediat
  • Li W, Tang Y, Liu H, et al. (2008). Probing ligand binding modes of human cytochrome P450 2J2 by homology modeling, molecular dynamics simulation, and flexible molecular docking. Proteins 71:938–949
  • Li YC, Chiang J. (1991). The expression of a catalytically active cholesterol 7 alpha-hydroxylase cytochrome P450 in Escherichia coli. J Biol Chem 266:19186–19191
  • Libby P. (2002). Inflammation in atherosclerosis. Nature 420:868–874
  • Liu KH, Kim MG, Lee DJ, et al. (2006). Characterization of ebastine, hydroxyebastine, and carebastine metabolism by human liver microsomes and expressed cytochrome P450 enzymes: Major roles for CYP2J2 and CYP3A. Drug Metab Dispos 34:1793–1797
  • Liu L, Chen C, Gong W, et al. (2011). Epoxyeicosatrienoic acids attenuate reactive oxygen species level, mitochondrial dysfunction, caspase activation, and apoptosis in carcinoma cells treated with arsenic trioxide. J Pharmacol Exp Ther 339:451–463
  • Liu PY, Li YH, Chao TH, et al. (2007). Synergistic effect of cytochrome P450 epoxygenase CYP2J2*7 polymorphism with smoking on the onset of premature myocardial infarction. Atherosclerosis 195:199–206
  • Liu Y, Zhang Y, Schmelzer K, et al. (2005). The antiinflammatory effect of laminar flow: The role of PPARgamma, epoxyeicosatrienoic acids, and soluble epoxide hydrolase. Proc Natl Acad Sci U S A 102:16747–16752
  • Loch D, Hoey A, Morisseau C, et al. (2007). Prevention of hypertension in DOCA-salt rats by an inhibitor of soluble epoxide hydrolase. Cell Biochem Biophys 47:87–98
  • Lu T, Ye D, Wang X, et al. (2006). Cardiac and vascular KATP channels in rats are activated by endogenous epoxyeicosatrienoic acids through different mechanisms. J Physiol 575:627–644
  • Lucas D, Goulitquer S, Marienhagen J, et al. (2010). Stereoselective epoxidation of the last double bond of polyunsaturated fatty acids by human cytochromes P450. J Lipid Res 51:1125–1133
  • Lucey MR, Abdelmalek MF, Gagliardi R, et al. (2005). A comparison of tacrolimus and cyclosporine in liver transplantation: Effects on renal function and cardiovascular risk status. Am J Transplant 5:1111–1119
  • Ma J, Bradbury JA, King L, et al. (2002). Molecular cloning and characterization of mouse CYP2J6, an unstable cytochrome P450 isoform. Biochem Pharmacol 64:1447–1460
  • Ma J, Graves J, Bradbury JA, et al. (2004). Regulation of mouse renal CYP2J5 expression by sex hormones. Mol Pharmacol 65:730–743
  • Ma J, Qu W, Scarborough PE, et al. (1999). Molecular cloning, enzymatic characterization, developmental expression, and cellular localization of a mouse cytochrome P450 highly expressed in kidney. J Biol Chem 274:17777–17788
  • Ma J, Ramachandran S, Fiedorek FT, Jr, Zeldin DC. (1998). Mapping of the CYP2J cytochrome P450 genes to human chromosome 1 and mouse chromosome 4. Genomics 49:152–155
  • Macica C, Balazy M, Falck J, et al. (1993). Characterization of cytochrome P-450-dependent arachidonic acid metabolism in rabbit intestine. Am J Physiol – Gastrointestinal Liver Physiol 265:G735–G741
  • Madhun ZT, Goldthwait DA, McKay D, et al. (1991). An epoxygenase metabolite of arachidonic acid mediates angiotensin II-induced rises in cytosolic calcium in rabbit proximal tubule epithelial cells. J Clin Invest 88:456–461
  • Maier KG, Roman RJ. (2001). Cytochrome P450 metabolites of arachidonic acid in the control of renal function. Curr Opin Nephrol Hypertens 10:81–87
  • Makita K, Takahashi K, Karara A, et al. (1994). Experimental and/or genetically controlled alterations of the renal microsomal cytochrome P450 epoxygenase induce hypertension in rats fed a high salt diet. J Clin Invest 94:2414–2420
  • Marciante KD, Totah RA, Heckbert SR, et al. (2008). Common variation in cytochrome P450 epoxygenase genes and the risk of incident nonfatal myocardial infarction and ischemic stroke. Pharmacogenet Genomics 18:535–543
  • Marden NY, Fiala-Beer E, Xiang SH, urray M. (2003). Role of activator protein-1 in the down-regulation of the human CYP2J2 gene in hypoxia. Biochem J 373:669–680
  • Marden NY, Murray M. (2005). Characterization of a c-Jun-responsive module in the 5'-flank of the human CYP2J2 gene that regulates transactivation. Biochem J 391:631–640
  • Marhaba R, Zoller M. (2004). CD44 in cancer progression: Adhesion, migration and growth regulation. J Mol Histol 35:211–231
  • Matsuda M, Sakashita M, Mizuki Y, et al. (1994). Comparative pharmacokinetics of the histamine H1-receptor antagonist ebastine and its active metabolite carebastine in rats, guinea pigs, dogs and monkeys. Arzneimittelforschung 44:55–59
  • Matsumoto S, Hirama T, Kim H, et al. (2003). In vitro inhibition of human small intestinal and liver microsomal astemizole O-demethylation: Different contribution of CYP2J2 in the small intestine and liver. Xenobiotica 33:615–623
  • Matsumoto S, Hirama T, Matsubara T, et al. (2002). Involvement of CYP2J2 on the intestinal first-pass metabolism of antihistamine drug, astemizole. Drug Metab Dispos 30:1240–1245
  • Matsumoto S, Yamazoe Y. (2001). Involvement of multiple human cytochromes P450 in the liver microsomal metabolism of astemizole and a comparison with terfenadine. Brit J Clin Pharmacol 51:133–142
  • Matsunaga M, Uemura Y, Yonemoto Y, et al. (1997). Long-lasting muscle relaxant activity of eperisone hydrochloride after percutaneous administration in rats. Jpn J Pharmacol 73:215–220
  • McGiff JC, Quilley J. (1999). 20-HETE and the kidney: Resolution of old problems and new beginnings. Am J Physiol 277:R607–623
  • Medhora M, Daniels J, Mundey K, et al. (2003). Epoxygenase-driven angiogenesis in human lung microvascular endothelial cells. Am J Physiol Heart Circ Physiol 284:H215–224
  • Messina A, Nencioni S, Gervasi PG, et al. (2010). Molecular cloning and enzymatic characterization of sheep CYP2J. Xenobiotica 40:109–118
  • Messina A, Siniscalco A, Puccinelli E, et al. (2012). Cloning and tissues expression of the pig CYP1B1 and CYP2J34. Res Vet Sci 92:438–443
  • Meuldermans W, Hendrickx J, Lauwers W, et al. (1986). Excretion and biotransformation of astemizole in rats, guinea-pigs, dogs, and man. Drug Dev Res 8:37–51
  • Miao L, Klein MA, Travers KE, et al. (1997). Acute and chronic cocaine exposure can produce myocardial ischemia and infarction in Yucatan swine. J Cardiovasc Pharmacol 29:145–155
  • Michaelis UR, Fisslthaler B, Medhora M, et al. (2003). Cytochrome P450 2C9-derived epoxyeicosatrienoic acids induce angiogenesis via cross-talk with the epidermal growth factor receptor (EGFR). FASEB J 17:770–772
  • Michaud V, Frappier M, Dumas MC, Turgeon J. (2010). Metabolic activity and mRNA levels of human cardiac CYP450s involved in drug metabolism. PLoS One 5:e15666
  • Mihara K, Matsumura M, Yoshioka E, et al. (2001). Intestinal first-pass metabolism of eperisone in the rat. Pharm Res 18:1131–1137
  • Minamiyama Y, Takemura S, Imaoka S, et al. (2007). Cytochrome P450 is responsible for nitric oxide generation from NO-aspirin and other organic nitrates. Drug Metab Pharmacokinet 22:15–19
  • Minet E, Michel G, Mottet D, et al. (2001). c-JUN gene induction and AP-1 activity is regulated by a JNK-dependent pathway in hypoxic HepG2 cells. Exp Cell Res 265:114
  • Minuz P, Jiang H, Fava C, et al. (2008). Altered release of cytochrome p450 metabolites of arachidonic acid in renovascular disease. Hypertension 51:1379–1385
  • Mishra RR, Adhikary G, Simonson MS, et al. (1998). Role of c- fos in hypoxia-induced AP-1 cis-element activity and tyrosine hydroxylase gene expression. Mol Brain Res 59:74–83
  • Moran JH, Mitchell LA, Bradbury JA, et al. (2000). Analysis of the cytotoxic properties of linoleic acid metabolites produced by renal and hepatic P450s. Toxicol Appl Pharmacol 168:268–279
  • Moreland KT, Procknow JD, Sprague RS, et al. (2007). Cyclooxygenase (COX)-1 and COX-2 participate in 5,6-epoxyeicosatrienoic acid-induced contraction of rabbit intralobar pulmonary arteries. J Pharmacol Exp Therap 321:446–454
  • Morgan ET. (2001). Regulation of cytochrome p450 by inflammatory mediators: Why and how? Drug Metab Dispos 29:207–212
  • Morin C, Sirois M, Echave V, et al. (2007). Epoxyeicosatrienoic acid relaxing effects involve Ca2+-activated K+ channel activation and CPI-17 dephosphorylation in human bronchi. Am J Respir Cell Mol Biol 36:633
  • Moss AJ, Morganroth J. (1999). Cardiac effects of ebastine and other antihistamines in humans. Drug Saf 21:69–80; discussion 81–67
  • Mott JL. (2009). MicroRNAs involved in tumor suppressor and oncogene pathways: Implications for hepatobiliary neoplasia. Hepatology 50:630–637
  • Murray G, Barnes T, Sewell H, et al. (1988). The immunocytochemical localisation and distribution of cytochrome P-450 in normal human hepatic and extrahepatic tissues with a monoclonal antibody to human cytochrome P-450. Brit J Clin Pharmacol 25:465–475
  • Naccarelli GV, Wolbrette DL, Dell'Orfano JT, et al. (2000). Amiodarone: What have we learned from clinical trials? Clin Cardiol 23:73–82
  • Nagano O, Saya H. (2004). Mechanism and biological significance of CD44 cleavage. Cancer Sci 95:930–935
  • Nakayama K, Nitto T, Inoue T, Node K. (2008). Expression of the cytochrome P450 epoxygenase CYP2J2 in human monocytic leukocytes. Life Sci 83:339–345
  • Navar LG, Inscho EW, Majid SA, et al. (1996). Paracrine regulation of the renal microcirculation. Physiol Rev 76:425–536
  • Needleman P, Jakschik B, Morrison A, Lefkowith J. (1986). Arachidonic acid metabolism. Annu Rev Biochem 55:69–102
  • Nelson DR, Kamataki T, Waxman DJ, et al. (1993). The P450 superfamily: Update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature. DNA Cell Biol 12:1–51
  • Nelson DR, Zeldin DC, Hoffman SM, et al. (2004). Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants. Pharmacogenetics 14:1–18
  • Nguyen LT, Ramanathan M, Weinstock-Guttman B, et al. (2000). Detection of cytochrome P450 and other drug-metabolizing enzyme mRNAs in peripheral blood mononuclear cells using DNA arrays. Drug Metab Dispos 28:987–993
  • Nishimuta H, Sato K, Mizuki Y, et al. (2011). Species differences in intestinal metabolic activities of cytochrome P450 isoforms between cynomolgus monkeys and humans. Drug Metab Pharmacokinet 26:300–306
  • Nithipatikom K, Brody DM, Tang AT, et al. (2010). Inhibition of carcinoma cell motility by epoxyeicosatrienoic acid (EET) antagonists. Cancer Sci 101:2629–2636
  • Node K, Huo Y, Ruan X, et al. (1999). Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science 285:1276–1279
  • Node K, Ruan XL, Dai J, et al. (2001). Activation of Galpha s mediates induction of tissue-type plasminogen activator gene transcription by epoxyeicosatrienoic acids. J Biol Chem 276:15983–15989
  • Nusing RM, Schweer H, Fleming I, et al. (2007). Epoxyeicosatrienoic acids affect electrolyte transport in renal tubular epithelial cells: Dependence on cyclooxygenase and cell polarity. Am J Physiol Renal Physiol 293:F288–F298
  • O'Neil JD, Owen TJ, Wood VHJ, et al. (2008). Epstein–Barr virus-encoded EBNA1 modulates the AP-1 transcription factor pathway in nasopharyngeal carcinoma cells and enhances angiogenesis in vitro. J Gen Virol 89:2833–2842
  • Odintsova E, Sugiura T, Berditchevski F. (2000). Attenuation of EGF receptor signaling by a metastasis suppressor, the tetraspanin CD82/KAI-1. Curr Biol 10:1009–1012
  • Ohyama K, Nakajima M, Nakamura S, et al. (2000). A significant role of human cytochrome P450 2C8 in amiodarone N-deethylation: An approach to predict the contribution with relative activity factor. Drug Metab Dispos 28:1303–1310
  • Ohyama Y, Yamasaki T. (2004). Eight cytochrome P450s catalyze vitamin D metabolism. Front Biosci 9:3007–3018
  • Ojeda SR, Urbanski HF, Junier MP, Capdevila J. (1989). The role of arachidonic acid and its metabolites in the release of neuropeptidesa. Ann N Y Acad Sci 559:192–207
  • Ominato M, Satoh T, Katz AI. (1996). Regulation of Na-K-ATPase activity in the proximal tubule: Role of the protein kinase C pathway and of eicosanoids. J Membr Biol 152:235–243
  • Ouatas T, Salerno M, Palmieri D, Steeg PS. (2003). Basic and translational advances in cancer metastasis: Nm23. J Bioenerg Biomembr 35:73–79
  • Paine MF, Hart HL, Ludington SS, et al. (2006). The human intestinal cytochrome P450 “pie”. Drug Metab Dispos 34:880–886
  • Panigrahy D, Edin ML, Lee CR, et al. (2012). Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice. J Clin Invest 122:178–191
  • Panigrahy D, Kaipainen A, Huang S, et al. (2008). PPARalpha agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition. Proc Natl Acad Sci U S A 105:985–990
  • Parikh S, Gagne P, Miller V, et al. (2003). CYP2J2 and CYP4F12 are active for the metabolism of non-sedating antihistamines: Terfenadine and astemizole. Drug Metab Rev 35:190
  • Park SW, Heo DS, Sung MW. (2012). The shunting of arachidonic acid metabolism to 5-lipoxygenase and cytochrome p450 epoxygenase antagonizes the anti-cancer effect of cyclooxygenase-2 inhibition in head and neck cancer cells. Cell Oncol (Dordr) 35:1–8
  • Pascual JM. S., McKenzie A, Yankaskas JR, et al. (1998). Epoxygenase metabolites of arachidonic acid affect electrophysiologic properties of rat tracheal epithelial cells1. J Pharmacol Exp Therap 286:772–779
  • Peter Guengerich F. (1994). Catalytic selectivity of human cytochrome P450 enzymes: Relevance to drug metabolism and toxicity. Toxicol Lett 70:133–138
  • Pinto A, Abraham NG, Mullane KM. (1987). Arachidonic acid-induced endothelial-dependent relaxations of canine coronary arteries: Contribution of a cytochrome P-450-dependent pathway. J Pharmacol Exp Ther 240:856–863
  • Pokreisz P, Fleming I, Kiss L, et al. (2006). Cytochrome P450 epoxygenase gene function in hypoxic pulmonary vasoconstriction and pulmonary vascular remodeling. Hypertension 47:762–770
  • Polonikov AV, Ivanov VP, Solodilova MA, et al. (2007). Promoter polymorphism G-50T of a human CYP2J2 epoxygenase gene is associated with common susceptibility to asthma. Chest 132:120–126
  • Polonikov AV, Ivanov VP, Solodilova MA, et al. (2008). A common polymorphism G-50T in cytochrome P450 2J2 gene is associated with increased risk of essential hypertension in a Russian population. Dis Markers 24:119–126
  • Pozzi A, Ibanez MR, Gatica AE, et al. (2007). Peroxisomal proliferator-activated receptor-alpha-dependent inhibition of endothelial cell proliferation and tumorigenesis. J Biol Chem 282:17685–17695
  • Pozzi A, Macias-Perez I, Abair T, et al. (2005). Characterization of 5,6- and 8,9-epoxyeicosatrienoic acids (5,6- and 8,9-EET) as potent in vivo angiogenic lipids. J Biol Chem 280:27138–27146
  • Pozzi A, Popescu V, Yang S, et al. (2010). The anti-tumorigenic properties of peroxisomal proliferator-activated receptor alpha are arachidonic acid epoxygenase-mediated. J Biol Chem 285:12840–12850
  • Proctor KG, Falck JR, Capdevila J. (1987). Intestinal vasodilation by epoxyeicosatrienoic acids: Arachidonic acid metabolites produced by a cytochrome P450 monooxygenase. Circ Res 60:50–59
  • Pucci L, Lucchesi D, Chirulli V, et al. (2003). Cytochrome P450 2J2 polymorphism in healthy Caucasians and those with diabetes mellitus. Am J Pharmacogenomics 3:355–358
  • Qu W, Bradbury JA, Tsao CC, et al. (2001). Cytochrome P450 CYP2J9, a new mouse arachidonic acid omega-1 hydroxylase predominantly expressed in brain. J Biol Chem 276:25467–25479
  • Qu W, Rippe RA, Ma J, et al. (1998). Nutritional status modulates rat liver cytochrome P450 arachidonic acid metabolism. Mol Pharmacol 54:504–513
  • Ray JM, & Stetler-Stevenson WG. (1994). The role of matrix metalloproteases and their inhibitors in tumour invasion, metastasis and angiogenesis. Eur Respir J 7:2062–2072
  • Ren S, Zeng J, Mei Y, et al. (2013). Discovery and Characterization of Novel, Potent, and Selective Cytochrome P450 2J2 Inhibitors. Drug Metab Dispos 41:60–71
  • Rendic S, Nolteernsting E, Schänzer W. (1999). Metabolism of anabolic steroids by recombinant human cytochrome P450 enzymes: Gas chromatographic–mass spectrometric determination of metabolites. J Chromatogr B: Biomed Sci Appl 735:73–83
  • Richards DM, Brogden RN, Heel RC, et al. (1984). Astemizole: A review of its pharmacodynamic properties and therapeutic efficacy. Drugs 28:38–61
  • Rifkind AB, Lee C, Chang TKH, Waxman DJ. (1995). Arachidonic acid metabolism by human cytochrome P450s 2C8, 2C9, 2E1, and 1A2: Regioselective oxygenation and evidence for a role for CYP2C enzymes in arachidonic acid epoxygenation in human liver microsomes. Arch Biochem Biophys 320:380–389
  • Rodrigues AD, Mulford DJ, Lee RD, et al. (1995). In vitro metabolism of terfenadine by a purified recombinant fusion protein containing cytochrome P4503A4 and NADPH-P450 reductase. Comparison to human liver microsomes and precision-cut liver tissue slices. Drug Metab Dispos 23:765–775
  • Roman RJ. (2002). P-450 metabolites of arachidonic acid in the control of cardiovascular function. Physiol Rev 82:131–185
  • Romero MF, Hopfer U, Madhun ZT, et al. (1991). Angiotensin II actions in the rabbit proximal tubule. Angiotensin II mediated signaling mechanisms and electrolyte transport in the rabbit proximal tubule. Ren Physiol Biochem 14:199–207
  • Sakaki T, Kagawa N, Yamamoto K, Inouye K. (2005). Metabolism of vitamin D3 by cytochromes P450. Front Biosci 10:119–134
  • Salvail D, Dumoulin M, Rousseau E. (1998). Direct modulation of tracheal Cl−-channel activity by 5, 6-and 11, 12-EET. Am J Physiol – Lung Cell Mol Physiol 275:L432–L441
  • Sampson VB, Rong NH, Han J, et al. (2007). MicroRNA let-7a down-regulates MYC and reverts MYC-induced growth in Burkitt lymphoma cells. Cancer Res 67:9762–9770
  • Sato M, Yokoyama U, Fujita T, et al. (2011). The roles of cytochrome p450 in ischemic heart disease. Curr Drug Metab 12:526–532
  • Savas U, Griffin KJ, Johnson EF. (1999). Molecular mechanisms of cytochrome P-450 induction by xenobiotics: An expanded role for nuclear hormone receptors. Mol Pharmacol 56:851–857
  • Scarborough PE, Ma J, Qu W, Zeldin DC. (1999). P450 subfamily CYP2J and their role in the bioactivation of arachidonic acid in extrahepatic tissues. Drug Metab Rev 31:205–234
  • Schaefer WR, Werner K, Schweer H, et al. (1997). Cytochrome P450 metabolites of arachidonic acid in human placenta. Prostaglandins 54:677–687
  • Schmeck B, Moog K, Zahlten J, et al. (2006). Streptococcus pneumoniae induced c-Jun-N-terminal kinase-and AP-1-dependent IL-8 release by lung epithelial BEAS-2B cells. Respir Res 7:7149–7155
  • Schwartzman M, Ferreri N, Carroll M, et al. (1985). Renal cytochrome P450-related arachidonate metabolite inhibits (Na+–K+) ATPase
  • Seubert J, Yang B, Bradbury JA, et al. (2004). Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway. Circ Res 95:506–514
  • Shimada T, Yamazaki H, Mimura M, et al. (1994). Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: Studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Therap 270:414–423
  • Siest G, Jeannesson E, Marteau JB, et al. (2008). Transcription factor and drug-metabolizing enzyme gene expression in lymphocytes from healthy human subjects. Drug Metab Dispos 36:182–189
  • Smith HE, Jones JP, 3rd, Kalhorn TF, et al. (2008). Role of cytochrome P450 2C8 and 2J2 genotypes in calcineurin inhibitor-induced chronic kidney disease. Pharmacogenet Genomics 18:943–953
  • Spiecker M, Darius H, Hankeln T, et al. (2004). Risk of coronary artery disease associated with polymorphism of the cytochrome P450 epoxygenase CYP2J2. Circulation 110:2132–2136
  • Spiecker M, Liao J. (2006). Cytochrome P450 epoxygenase CYP2J2 and the risk of coronary artery disease. Trends Cardiovasc Med 16:204–208
  • Spiecker M, Liao JK. (2005). Vascular protective effects of cytochrome p450 epoxygenase-derived eicosanoids. Arch Biochem Biophys 433:413–420
  • Steeg PS, Bevilacqua G, Kopper L, et al. (1988). Evidence for a novel gene associated with low tumor metastatic potential. J Natl Cancer Inst 80:200–204
  • Stephenson AH, Sprague RS, Lonigro AJ. (1998). 5,6-Epoxyeicosatrienoic acid reduces increases in pulmonary vascular resistance in the dog. Am J Physiol – Heart Circulatory Physiol 275:H100–H109
  • Stephenson AH, Sprague RS, Losapio JL, Lonigro AJ. (2003). Differential effects of 5, 6-EET on segmental pulmonary vasoactivity in the rabbit. Am J Physiol – Heart Circulatory Physiol 284:H2153–H2161
  • Stresser DM, Broudy MI, Ho T, et al. (2004). Highly selective inhibition of human CYP3Aa in vitro by azamulin and evidence that inhibition is irreversible. Drug Metab Dispos 32:105–112
  • Sun P, Liu W, Lin DH, et al. (2009). Epoxyeicosatrienoic acid activates BK channels in the cortical collecting duct. J Am Soc Nephrol 20:513–523
  • Takahashi K, Capdevila J, Karara A, et al. (1990). Cytochrome P-450 arachidonate metabolites in rat kidney: Characterization and hemodynamic responses. Am J Physiol – Renal Physiol 258:F781–F789
  • Takeshita H, Tsubota E, Takatsuka H, et al. (2008). Cytochrome P450 2J2*7 polymorphisms in Japanese, Mongolians and Ovambos. Cell Biochem Funct 26:813–816
  • Tan JZ, Kaley G, Gurtner GH. (1997). Nitric oxide and prostaglandins mediate vasodilation to 5,6-EET in rabbit lung. Adv Exp Med Biol 407:561–566
  • Theken KN, Deng Y, Kannon MA, et al. (2011). Activation of the acute inflammatory response alters cytochrome P450 expression and eicosanoid metabolism. Drug Metab Dispos 39:22–29
  • Theken KN, Lee CR. (2007). Genetic variation in the cytochrome P450 epoxygenase pathway and cardiovascular disease risk. Pharmacogenomics 8:1369–1383
  • Thelen K, Dressman JB. (2009). Cytochrome P450-mediated metabolism in the human gut wall. J Pharm Pharmacol 61:541–558
  • Thum T, Borlak J. (2000). Gene expression in distinct regions of the heart. Lancet 355:979–983
  • Turk J, Wolf BA, Comens PG, et al. (1985). Arachidonic acid metabolism in isolated pancreatic islets. IV. Negative ion-mass spectrometric quantitation of monooxygenase product synthesis by liver and islets. Biochim Biophys Acta 835:1–17
  • Turpie AG. (2007). Oral, direct factor Xa inhibitors in development for the prevention and treatment of thromboembolic diseases. Arterioscler Thromb Vasc Biol 27:1238–1247
  • Uno Y, Hosaka S, Matsuno K, et al. (2007). Characterization of cynomolgus monkey cytochrome P450 (CYP) cDNAs: Is CYP2C76 the only monkey-specific CYP gene responsible for species differences in drug metabolism? Arch Biochem Biophys 466:98–105
  • Vincenti F, Ramos E, Brattstrom C, et al. (2001). Multicenter trial exploring calcineurin inhibitors avoidance in renal transplantation. Transplantation 71:1282–1287
  • Walles M, Thum T, Levsen K, Borlak J. (2002). Verapamil: New insight into the molecular mechanism of drug oxidation in the human heart. J Chromatogr A 970:117–130
  • Wang CP, Hung WC, Yu TH, et al. (2010). Genetic variation in the G-50T polymorphism of the cytochrome P450 epoxygenase CYP2J2 gene and the risk of younger onset type 2 diabetes among Chinese population: Potential interaction with body mass index and family history. Exp Clin Endocrinol Diabetes 118:346–352
  • Wang D, Hirase T, Nitto T, et al. (2009). Eicosapentaenoic acid increases cytochrome P-450 2J2 gene expression and epoxyeicosatrienoic acid production via peroxisome proliferator-activated receptor gamma in endothelial cells. J Cardiol 54:368–374
  • Wang H, Jiang Y, Liu Y, et al. (2006). CYP2J2*7 single nucleotide polymorphism in a Chinese population. Clin Chim Acta 365:125–128
  • Wang HX, Zhang DM, Zeng XJ, et al. (2012). Upregulation of cytochrome P450 2J3/11, 12-epoxyeicosatrienoic acid inhibits apoptosis in neonatal rat cardiomyocytes by a caspase-dependent pathway. Cytokine
  • Wang JF, Yang Y, Sullivan MF, et al. (2002). Induction of cardiac cytochrome p450 in cocaine-treated mice. Exp Biol Med (Maywood) 227:182–188
  • Wang L, Yao J, Chen L, et al. (2007). Expression and possible functional roles of cytochromes P450 2J1 (zfCyp 2J1) in zebrafish. Biochem Biophys Res Commun 352:850–855
  • Wang L, Zhang D, Raghavan N, et al. (2010). In vitro assessment of metabolic drug-drug interaction potential of apixaban through cytochrome P450 phenotyping, inhibition, and induction studies. Drug Metab Dispos 38:448–458
  • Watkins PB, Wrighton SA, Schuetz EG, et al. (1987). Identification of glucocorticoid-inducible cytochromes P-450 in the intestinal mucosa of rats and man. J Clin Invest 80:1029–1036
  • Waxman DJ. (1999). P450 gene induction by structurally diverse xenochemicals: Central role of nuclear receptors CAR, PXR, and PPAR. Arch Biochem Biophys 369:11–23
  • Werner K, Schaefer WR, Schweer H, et al. (2002). Characterization and identification of cytochrome P450 metabolites of arachidonic acid released by human peritoneal macrophages obtained from the pouch of Douglas. Prostaglandins Leukot Essent Fatty Acids 67:397–404
  • Williams JM, Sharma M, Anjaiahh S, et al. (2007). Role of endogenous CYP450 metabolites of arachidonic acid in maintaining the glomerular protein permeability barrier. Am J Physiol Renal Physiol 293:F501–F505
  • Winters DK, Cederbaum AI. (1992). Time course characterization of the induction of cytochrome P-450 2E1 by pyrazole and 4-methylpyrazole. Biochim Biophys Acta 1117:15–24
  • Wolf BA, Colca JR, Turk J, et al. (1988). Regulation of Ca2+ homeostasis by islet endoplasmic reticulum and its role in insulin secretion. Am J Physiol 254:E121–136
  • Wolf BA, Turk J, Sherman WR, McDaniel ML. (1986). Intracellular Ca2+ mobilization by arachidonic acid. Comparison with myo-inositol 1,4,5-trisphosphate in isolated pancreatic islets. J Biol Chem 261:3501–3511
  • Wu D, Cederbaum AI. (1994). Characterization of pyrazole and 4-methylpyrazole induction of cytochrome P4502E1 in rat kidney. J Pharmacol Exp Ther 270:407–413
  • Wu S, Chen W, Murphy E, et al. (1997). Molecular cloning, expression, and functional significance of a cytochrome P450 highly expressed in rat heart myocytes. J Biol Chem 272:12551–12559
  • Wu S, Moomaw CR, Tomer KB, et al. (1996). Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart. J Biol Chem 271:3460–3468
  • Wu SN, Zhang Y, Gardner CO, et al. (2007). Evidence for association of polymorphisms in CYP2J2 and susceptibility to essential hypertension. Ann Hum Genet 71:519–525
  • Xiao B, Li X, Yan J, et al. (2010). Overexpression of cytochrome P450 epoxygenases prevents development of hypertension in spontaneously hypertensive rats by enhancing atrial natriuretic peptide. J Pharmacol Exp Ther 334:784–794
  • Xie Q, Zhang QY, Zhang Y, et al. (2000). Induction of mouse CYP2J by pyrazole in the eye, kidney, liver, lung, olfactory mucosa, and small intestine, but not in the heart. Drug Metab Dispos 28:1311–1316
  • Xu X, Zhang XA, Wang DW. (2011a). The roles of CYP450 epoxygenases and metabolites, epoxyeicosatrienoic acids, in cardiovascular and malignant diseases. Adv Drug Deliv Rev 63:597–609
  • Xu Y, Ding H, Peng J, et al. (2011b). Association between polymorphisms of CYP2J2 and EPHX2 genes and risk of coronary artery disease. Pharmacogenet Genomics 21:489–494
  • Yaghi A, Bend JR, Webb CD, et al. (2004). Excess nitric oxide decreases cytochrome P-450 2J4 content and P-450-dependent arachidonic acid metabolism in lungs of rats with acute pneumonia. Am J Physiol Lung Cell Mol Physiol 286:L1260–L1267
  • Yaghi A, Bradbury JA, Zeldin DC, et al. (2003). Pulmonary cytochrome P-450 2J4 is reduced in a rat model of acute Pseudomonas pneumonia. Am J Physiol – Lung Cell Mol Physiol 285:L1099–L1105
  • Yaghi A, Webb CD, Scott JA, et al. (2001). Cytochrome P450 metabolites of arachidonic acid but not cyclooxygenase-2 metabolites contribute to the pulmonary vascular hyporeactivity in rats with acute Pseudomonas pneumonia. J Pharmacol Exp Ther 297:479–488
  • Yamaguchi T, Hashizume T, Matsuda M, et al. (1994). Pharmacokinetics of the H1-receptor antagonist ebastine and its active metabolite carebastine in healthy subjects. Arzneimittelforschung 44:59–64
  • Yamasaki T, Izumi S, Ide H, Ohyama Y. (2004). Identification of a novel rat microsomal vitamin D3 25-hydroxylase. J Biol Chem 279:22848–22856
  • Yang B, Graham L, Dikalov S, et al. (2001). Overexpression of cytochrome P450 CYP2J2 protects against hypoxia-reoxygenation injury in cultured bovine aortic endothelial cells. Mol Pharmacol 60:310–320
  • Ye D, Zhang D, Oltman C, et al. (2002). Cytochrome p-450 epoxygenase metabolites of docosahexaenoate potently dilate coronary arterioles by activating large-conductance calcium-activated potassium channels. J Pharmacol Exp Ther 303:768–776
  • Yokoyama M, Origasa H, Matsuzaki M, et al. (2007). Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): A randomised open-label, blinded endpoint analysis. Lancet 369:1090–1098
  • Yoo HH, Kim NS, Lee J, et al. (2009). Characterization of human cytochrome P450 enzymes involved in the biotransformation of eperisone. Xenobiotica 39:1–10
  • Young RA, Mehendale HM. (1986). In vitro metabolism of amiodarone by rabbit and rat liver and small intestine. Drug Metab Dispos 14:423–429
  • Yu GG, Zeng XJ, Wang HX, et al. (2011). Cytochrome P450 2J3/epoxyeicosatrienoic acids mediate the cardioprotection induced by ischaemic post-conditioning, but not preconditioning, in the rat. Clin Exp Pharmacol Physiol 38:63–70
  • Yu Z, Huse LM, Adler P, et al. (2000). Increased CYP2J expression and epoxyeicosatrienoic acid formation in spontaneously hypertensive rat kidney. Mol Pharmacol 57:1011–1020
  • Yuan X, Xu C, Pan Z, et al. (2006). Butylated hydroxyanisole regulates ARE-mediated gene expression via Nrf2 coupled with ERK and JNK signaling pathway in HepG2 cells. Mol Carcinog 45:841–850
  • Yun CH, Okerholm RA, Guengerich FP. (1993). Oxidation of the antihistaminic drug terfenadine in human liver microsomes. Role of cytochrome P-450 3A (4) in N-dealkylation and C-hydroxylation. Drug Metab Dispos 21:403–409
  • Zeldin DC. (2001). Epoxygenase pathways of arachidonic acid metabolism. J Biol Chem 276:36059–36062
  • Zeldin DC, Foley J, Boyle JE, et al. (1997a). Predominant expression of an arachidonate epoxygenase in islets of Langerhans cells in human and rat pancreas. Endocrinology 138:1338–1346
  • Zeldin DC, Foley J, Goldsworthy SM, et al. (1997b). CYP2J subfamily cytochrome P450s in the gastrointestinal tract: Expression, localization, and potential functional significance. Mol Pharmacol 51:931–943
  • Zeldin DC, Foley J, Ma J, et al. (1996). CYP2J subfamily P450s in the lung: Expression, localization, and potential functional significance. Mol Pharmacol 50:1111–1117
  • Zeldin DC, Plitman JD, Kobayashi J, et al. (1995). The rabbit pulmonary cytochrome P450 arachidonic acid metabolic pathway: Characterization and significance. J Clin Invest 95:2150–2160
  • Zeldin DC, Wu S, Ma J. (1997c). CYP 2 J subfamily P-450s: Physiologically relevant hemoproteins active in the metabolism of arachidonic acid in hepatic and extrahepatic tissues. Rev Toxicol 1:1–32
  • Zhang L, Ding H, Yan J, et al. (2008). Genetic variation in cytochrome P450 2J2 and soluble epoxide hydrolase and risk of ischemic stroke in a Chinese population. Pharmacogenet Genomics 18:45–51
  • Zhang QY, Ding X, Dunbar D, et al. (1999a). Induction of rat small intestinal cytochrome P-450 2J4. Drug Metab Dispos 27:1123–1127
  • Zhang QY, Ding X, Kaminsky LS. (1997). CDNA cloning, heterologous expression, and characterization of rat intestinal CYP2J4. Arch Biochem Biophys 340:270–278
  • Zhang QY, Dunbar D, Ostrowska A, et al. (1999b). Characterization of human small intestinal cytochromes P-450. Drug Metab Dispos 27:804–809
  • Zhang QY, Raner G, Ding X, et al. (1998). Characterization of the cytochrome P450 CYP2J4: Expression in rat small intestine and role in retinoic acid biotransformation from retinal. Arch Biochem Biophys 353:257–264
  • Zhang Y, Oltman CL, Lu T, et al. (2001). EET homologs potently dilate coronary microvessels and activate BK(Ca) channels. Am J Physiol Heart Circ Physiol 280:H2430–H2440
  • Zhao G, Tu L, Li X, et al. (2012). Delivery of AAV2-CYP2J2 protects remnant kidney in the 5/6-nephrectomized rat via inhibition of apoptosis and fibrosis. Hum Gene Ther
  • Zhou Y, Chang HH, Du J, et al. (2005). Renal epoxyeicosatrienoic acid synthesis during pregnancy. Am J Physiol Renal Physiol 288:F221–F226
  • Zhu D, Bousamra II M, Zeldin DC, et al. (2000a). Epoxyeicosatrienoic acids constrict isolated pressurized rabbit pulmonary arteries. Am J Physiol – Lung Cell Mol Physiol 278:L335–L343
  • Zhu D, Falck JR, Bousamra M, et al. (2000b). Cytochrome P450 isoforms are present in airway microsomes and P450 metabolites modulate human bronchial tone (Abstract). Am J Respir Crit Care Med 161
  • Zhu J, Deluca HF. (2012). Vitamin D 25-hydroxylase – Four decades of searching, are we there yet? Arch Biochem Biophys 523:30–36
  • Zordoky BN, Anwar-Mohamed A, Aboutabl ME, El-Kadi AO. (2010). Acute doxorubicin cardiotoxicity alters cardiac cytochrome P450 expression and arachidonic acid metabolism in rats. Toxicol Appl Pharmacol 242:38–46
  • Zordoky BN, Anwar-Mohamed A, Aboutabl ME, El-Kadi AO. (2011). Acute doxorubicin toxicity differentially alters cytochrome P450 expression and arachidonic acid metabolism in rat kidney and liver. Drug Metab Dispos 39:1440–1450
  • Zordoky BN, El-Kadi AO. (2010). Effect of cytochrome P450 polymorphism on arachidonic acid metabolism and their impact on cardiovascular diseases. Pharmacol Ther 125:446–463
  • Zordoky BNM., Aboutabl ME, El-Kadi AO. S. (2008). Modulation of cytochrome P450 gene expression and arachidonic acid metabolism during isoproterenol-induced cardiac hypertrophy in rats. Drug Metab Dispos 36:2277–2286
  • Zou AP, Fleming JT, Falck JR, et al. (1996). Stereospecific effects of epoxyeicosatrienoic acids on renal vascular tone and K(+)-channel activity. Am J Physiol 270:F822–F832

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.