880
Views
28
CrossRef citations to date
0
Altmetric
Review Article

CYP2J2 – regulation, function and polymorphism

Pages 351-368 | Received 04 Apr 2016, Accepted 06 May 2016, Published online: 10 Jun 2016

References

  • 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.
  • Aitken AE, Morgan ET. (2007). Gene-specific effects of inflammatory cytokines on cytochrome P450 2C, 2B6 and 3A4 mRNA levels in human hepatocytes. Drug Metab Dispos 35:1687–1693.
  • Aitken AE, Richardson TA, Morgan ET. (2006). Regulation of drug-metabolizing enzymes and transporters in inflammation. Annu Rev Pharmacol Toxicol 46:123–149.
  • 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 16:1027–1031.
  • 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 40:2126–2135.
  • Arnold C, Markovic M, Blossey K, et al. (2010). Arachidonic acid-metabolizing cytochrome P450 enzymes are targets of ω-3 fatty acids. J Biol Chem 285:32720–32733.
  • Askari AA, Thomson S, Edin ML, et al. (2014). Basal and inducible anti-inflammatory epoxygenase activity in endothelial cells. Biochem Biophys Res Commun 446:633–637.
  • Backlund M, Johansson I, Mkrtchian S, Ingelman-Sundberg M. (1997). Signal transduction-mediated activation of the aryl hydrocarbon receptor in rat hepatoma H4IIE cells. J Biol Chem 272:31755–31763.
  • Bao MH, Feng X, Zhang YW. (2013). Let-7 in cardiovascular diseases, heart development and cardiovascular differentiation from stem cells. Int J Mol Sci 14:23086–23102.
  • Batchu SN, Chaudhary KR, El-Sikhry H, et al. (2012). Role of PI3Kα and sarcolemmal ATP-sensitive potassium channels in epoxyeicosatrienoic acid mediated cardioprotection. J Mol Cell Cardiol 53:43–52.
  • Behm DJ, Ogbonna A, Wu C, et al. (2009). Epoxyeicosatrienoic acids function as selective, endogenous antagonists of native thromboxane receptors: Identification of a novel mechanism of vasodilation. J Pharmacol Exp Ther 328:231–239.
  • Behmoaras J, Diaz AG, Venda L, et al. (2015). Macrophage epoxygenase determines a profibrotic transcriptome signature. J Immunol 194:4705–4716.
  • 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.
  • Bogoyevitch MA, Court NW. (2004). Counting on mitogen-activated protein kinases-ERKs 3, 4, 5, 6, 7 and 8. Cell Signal 16:1345–1354.
  • 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.
  • Boutros T, Chevet E, Metrakos P. (2008). Mitogen-activated protein (MAP) kinase/MAP kinase phosphatase regulation: Roles in cell growth, death, and cancer. Pharmacol Rev 60:261–310.
  • Bryan HK, Olayanju A, Goldring CG, Park BK. (2013). The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. Biochem Pharmacol 85:705–717.
  • Bystrom J, Thomson SJ, Johansson J, et al. (2013). Inducible CYP2J2 and its product 11,12-EET promotes bacterial phagocytosis: A role for CYP2J2 deficiency in the pathogenesis of Crohn's disease? PLoS One 8:e75107.
  • Campbell WB, Fleming I. (2010). Epoxyeicosatrienoic acids and endothelium-dependent responses. Pflugers Arch Eur J Physiol 459:881–895.
  • Cantrill E, Murray M, Mehta I, Farrell GC. (1989). Down-regulation of the male-specific steroid 16α-hydroxylase, cytochrome P-450UT-A, in male rats with portal bypass: Relevance to estradiol accumulation and impaired drug metabolism in hepatic cirrhosis. J Clin Invest 83:1211–1216.
  • Capdevila JH, Falck JR, Harris RC. (2000). Cytochrome P450 and arachidonic acid bioactivation. Molecular and functional properties of the arachidonate monooxygenase. J Lipid Res 41:163–181.
  • 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 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, Xu R, Zhang S, et al. (2015). CYP2J2 overexpression attenuates nonalcoholic fatty liver disease induced by high-fat diet in mice. Am J Physiol Endocrinol Metab 308:E97–E110.
  • Chen JK, Capdevila J, Harris RC. (2001). Cytochrome P450 epoxygenase metabolism of arachidonic acid inhibits apoptosis. Mol Cell Biol 21:6322–6331.
  • Chen JK, Falck JR, Reddy KM, et al. (1998). Epoxyeicosatrienoic acids and their sulfonimide derivatives stimulate tyrosine phosphorylation and induce mitogenesis in renal epithelial cells. J Biol Chem 273:29254–29261.
  • Chen JZ, Murray M, Liddle C, et al. (1995). Down-regulation of male-specific cytochrome P450s 2C11 and 3A2 in bile duct-ligated male rats: Importance to reduced hepatic content of cytochrome P450 in cholestasis. Hepatology 22:580–587.
  • Chen Y, Falck JR, Manthati VL, et al. (2011b). 20-Iodo-14,15-epoxyeicosa-8(Z)-enoyl-3-azidophenylsulfonamide: Photoaffinity labeling of a 14,15-epoxyeicosatrienoic acid receptor. Biochemistry 50:3840–3848.
  • Cheranov SY, Karpurapu M, Wang D, et al. (2008). An essential role for SRC-activated STAT-3 in 14,15-EET-induced VEGF expression and angiogenesis. Blood 111:5581–5591.
  • Cizkova K, Konieczna A, Erdosova B, Ehrmann J. (2014). Time-dependent expression of cytochrome P450 epoxygenases during human prenatal development. Organogenesis 10:53–61.
  • Clark JM, Diehl AM. (2003). Nonalcoholic fatty liver disease: An underrecognized cause of cryptogenic cirrhosis. JAMA 289:3000–3004.
  • Cui PH, Lee AC, Zhou F, Murray M. (2010). Impaired transactivation of the human CYP2J2 arachidonic acid epoxygenase gene in HepG2 cells subjected to nitrative stress. Br J Pharmacol 159:1440–1449.
  • Cui PH, Petrovic N, Murray M. (2011). The ω-3 epoxide of eicosapentaenoic acid inhibits endothelial cell proliferation by p38 MAP kinase activation and cyclin D1/CDK4 down-regulation. Br J Pharmacol 162:1143–1155.
  • Dai D, Zeldin DC, Blaisdell JA. (2001). Polymorphisms in human CYP2C8 decrease metabolism of the anticancer drug paclitaxel and arachidonic acid. Pharmacogenetics 11:597–607.
  • Daikh BE, Lasker JM, Raucy JL, Koop DR. (1994). Regio- and stereoselective epoxidation of arachidonic acid by human cytochromes P450 2C8 and 2C9. J Pharmacol Exp Ther 271:1427–1433.
  • Denison MS, Nagy SR. (2003). Activation of the aryl hydrocarbon receptor by structurally diverse exogenous and endogenous chemicals. Annu Rev Pharmacol Toxicol 43:309–334.
  • Dhanasekaran A, Al-Saghir R, Lopez B, et al. (2006). Protective effects of epoxyeicosatrienoic acids on human endothelial cells from the pulmonary and coronary vasculature. Am J Physiol Heart Circ Physiol 291:H517–H531.
  • 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.
  • Doecke CJ, Veronese ME, Pond SM, et al. (1991). Relationship between phenytoin and tolbutamide hydroxylations in human liver microsomes. Br J Clin Pharmacol 31:125–130.
  • 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, Hoffman SM, Keeney DS. (2004). Epidermal CYP2 family cytochromes P450. Toxicol Appl Pharmacol 195:278–287.
  • Duckett DR, Cameron MD. (2010). Metabolism considerations for kinase inhibitors in cancer treatment. Expert Opin Drug Metab Toxicol 6:1175–1193.
  • 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.
  • Dyari HRE, Rawling T, Bourget K, Murray M. (2014). Synthetic ω-3 epoxyfatty acids as anti-proliferative and pro-apoptotic agents in human breast cancer cells. J Med Chem 57:7459–7464.
  • Elmarakby AA, Quigley JE, Pollock DM, Imig JD. (2006). Tumor necrosis factor α blockade increases renal Cyp2c23 expression and slows the progression of renal damage in salt-sensitive hypertension. Hypertension 47:557–562.
  • Enayetallah AE, French RA, Grant DF. (2006). Distribution of soluble epoxide hydrolase, cytochrome P450 2C8, 2C9 and 2J2 in human malignant neoplasms. J Mol Histol 37:133–141.
  • 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.
  • Evangelista EA, Kaspera R, Mokadam NA, et al. (2013). Activity, inhibition, and induction of cytochrome P450 2J2 in adult human primary cardiomyocytes. Drug Metab Dispos 41:2087–2094.
  • Falck JR, Kodela R, Manne R, et al. (2009). 14,15-Epoxyeicosa-5,8,11-trienoic acid (14,15-EET) surrogates containing epoxide bioisosteres: Influence upon vascular relaxation and soluble epoxide hydrolase inhibition. J Med Chem 52:5069–5075.
  • Falck JR, Wallukat G, Puli N, et al. (2011). 17(R),18(S)-epoxyeicosatetraenoic acid, a potent eicosapentaenoic acid (EPA) derived regulator of cardiomyocyte contraction: Structure-activity relationships and stable analogues. J Med Chem 54:4109–4118.
  • Farrell GC, Murray M. (1990). Human cytochrome P450 isoforms. Their genetic heterogeneity and induction by omeprazole. Gastroenterology 99:885–889.
  • 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 Hypertension 28:294–299.
  • 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.
  • Fisher CD, Lickteig AJ, Augustine LM, et al. (2009). Hepatic cytochrome P450 enzyme alterations in humans with progressive stages of nonalcoholic fatty liver disease. Drug Metab Dispos 37:2087–2094.
  • 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.
  • Fleming I. (2004). Cytochrome P450 epoxygenases as EDHF synthase(s). Pharmacol Res 49:525–533.
  • Gaedigk A, Baker DW, Totah RA, et al. (2006). Variability of CYP2J2 expression in human fetal tissues. J Pharmacol Exp Ther 319:523–532.
  • Ghassabian S, Rawling T, Zhou F, et al. (2012). Role of human CYP3A4 in the biotransformation of sorafenib to its major oxidized metabolites. Biochem Pharmacol 84:215–223.
  • Hanahan D, Weinberg RA. (2011). Hallmarks of cancer: The next generation. Cell 144:646–674.
  • 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.
  • He K, Iyer KR, Hayes RN, et al. (1998). Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice. Chem Res Toxicol 11:252–259.
  • He K, Woolf TF, Hollenberg PF. (1999). Mechanism-based inactivation of cytochrome P-450-3A4 by mifepristone (RU486). J Pharmacol Exp Ther 288:791–797.
  • Hoffman 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.
  • Holla VR, Makita K, Zaphiropoulos PG, Capdevila JH. (1999). The kidney cytochrome P-450 2C23 arachidonic acid epoxygenase is upregulated during dietary salt loading. J Clin Invest 104:751–760.
  • Imig JD, Dimitropoulou C, Reddy DS, et al. (2008). Afferent arteriolar dilation to 11, 12-EET analogs involves PP2A activity and Ca2+-activated K + channels. Microcirculation 15:137–150.
  • Imig JD. (2000). Epoxygenase metabolites. Epithelial and vascular actions. Mol Biotechnol 16:233–251.
  • Inceoglu B, Schmelzer KR, Morisseau C, et al. (2007). Soluble epoxide hydrolase inhibition reveals novel biological functions of epoxyeicosatrienoic acids (EETs). Prostaglandins Other Lipid Mediat 82:42–49.
  • Inceoglu B, Wagner KM, Yang J, et al. (2012). Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes. Proc Natl Acad Sci USA 109:11390–11395.
  • Jarrar YB, Cho SA, Oh KS, et al. (2013). Identification of cytochrome P450s involved in the metabolism of arachidonic acid in human platelets. Prostagl Leukotr Essent Fatty Acids 89:227–324.
  • 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, Ning YG, Chen C, et al. (2007). Cytochrome P450 epoxygenase promotes human cancer metastasis. Cancer Res 67:6665–6674.
  • 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.
  • Kaspera R, Kirby BJ, Sahele T, et al. (2014). Investigating the contribution of CYP2J2 to ritonavir metabolism in vitro and in vivo. Biochem Pharmacol 91:109–118.
  • Katragadda D, Batchu SN, Cho WJ, et al. (2009). Epoxyeicosatrienoic acids limit damage to mitochondrial function following stress in cardiac cells. J Mol Cell Cardiol 46:867–875.
  • 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.
  • Kloth JS, Klümpen HJ, Yu H, et al. (2014). Predictive value of CYP3A and ABCB1 phenotyping probes for the pharmacokinetics of sunitinib: The ClearSun study. Clin Pharmacokinet 53:261–269.
  • 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, Zeldin DC, et al. (2007b). Selective, competitive and mechanism-based inhibitors of human cytochrome P450 2J2. Arch Biochem Biophys 464:155–168.
  • Leclerc J, Tournel G, Courcot-Ngoubo Ngangue E, et al. (2010). Profiling gene expression of whole cytochrome P450 superfamily in human bronchial and peripheral lung tissues: Differential expression in non-small cell lung cancers. Biochimie 92:292–306.
  • 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 HC, Lu T, Weintraub NL, et al. (1999). Effects of epoxyeicosatrienoic acids on sodium channels in isolated rat ventricular myocytes. J Physiol 519:153–168.
  • Lee KS, Liu JY, Wagner KM, et al. (2014). Optimized inhibitors of soluble epoxide hydrolase improve in vitro target residence time and in vivo efficacy. J Med Chem 57:7016–7030.
  • 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.
  • Lefer AM, Lefer DJ. (1993). Pharmacology of the endothelium in ischemia-reperfusion and circulatory shock. Annu Rev Pharmacol Toxicol 33:71–90.
  • Li R, Xu X, Chen C, et al. (2015). CYP2J2 attenuates metabolic dysfunction in diabetic mice by reducing hepatic inflammation via the PPARγ. Am J Physiol Endocrinol Metab 308:E270–E282.
  • 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.
  • Ma B, Xiong X, Chen C, et al. (2013). Cardiac-specific overexpression of CYP2J2 attenuates diabetic cardiomyopathy in male streptozotocin-induced diabetic mice. Endocrinology 154:2843–2856.
  • Mantovani A. (2009). Cancer: Inflaming metastasis. Nature 457:36–37.
  • 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.
  • Marcus CB, Murray M, Wilkinson CF. (1985). Spectral and inhibitory interactions of methylenedioxyphenyl and related compounds with purified isozymes of cytochrome P-450. Xenobiotica 15:351–362.
  • Marden NY, Fiala-Beer E, Xiang SH, Murray 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.
  • 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, 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.
  • McDougle DR, Kambalyal A, Meling DD, Das A. (2014). Endocannabinoids anandamide and 2-arachidonoylglycerol are substrates for human CYP2J2 epoxygenase. J Pharmacol Exp Ther 351:616–627.
  • 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–H224.
  • 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.
  • 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. Brain Res Mol Brain Res 59:74–83.
  • Morisseau C, Hammock BD. (2013). Impact of soluble epoxide hydrolase and epoxyeicosanoids on human health. Annu Rev Pharmacol Toxicol 53:37–58.
  • Morisseau C, Inceoglu B, Schmelzer K, et al. (2010). Naturally occurring monoepoxides of eicosapentaenoic acid and docosahexaenoic acid are bioactive antihyperalgesic lipids. J Lipid Res 51:3481–3490.
  • Munzenmaier DH, Harder DR. (2000). Cerebral microvascular endothelial cell tube formation: Role of astrocytic epoxyeicosatrienoic acid release. Am J Physiol Heart Circ Physiol 278:H1163–H1167.
  • Murray M, Field SL. (1992). Inhibition and metabolite complexation of rat hepatic microsomal cytochrome P450 by tricyclic antidepressants. Biochem Pharmacol 43:2065–2071.
  • Murray M, Hetnarski K, Wilkinson CF. (1985). Selective inhibitory interactions of alkoxymethylenedioxybenzenes towards mono-oxygenase activity in rat-hepatic microsomes. Xenobiotica 15:369–379.
  • Murray M, Zaluzny L, Farrell GC. (1987). Impaired androgen 16 alpha-hydroxylation in hepatic microsomes from carbon tetrachloride-cirrhotic male rats. Gastroenterology 93:141–147.
  • Murray M. (1984). In vitro effects of quinoline derivatives on cytochrome P-450 and aminopyrine N-demethylase activity in rat hepatic microsomes. Biochem Pharmacol 33:3277–3281.
  • 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.
  • Narjoz C, Favre A, McMullen J, et al. (2014). Important role of CYP2J2 in protein kinase inhibitor degradation: A possible role in intratumor drug disposition and resistance. PLoS One 9:e95532.
  • Nebot N, Crettol S, D’esposito F, et al. (2010). Participation of CYP2C8 and CYP3A4 in the N-demethylation of imatinib in human hepatic microsomes. Br J Pharmacol 161:1059–1069.
  • 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.
  • Node K, Huo Y, Ruan X, et al. (1999). Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Science 285:1276–1279.
  • O’Neill LAJ, Golenbock D, Bowie AG. (2013). The history of Toll-like receptors — redefining innate immunity. Nat Rev Immunol 13:453–460.
  • Ortiz de Montellano PR, Kunze KL. (1980). Self-catalyzed inactivation of hepatic cytochrome P-450 by ethynyl substrates. J Biol Chem 255:5578–5585.
  • 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.
  • Pavlov TS, Ilatovskaya DV, Levchenko V, et al. (2011). Effects of cytochrome P-450 metabolites of arachidonic acid on epithelial sodium channel (ENaC). Am J Physiol Ren Physiol 301:F672–F681.
  • Pidkovka N, Rao R, Mei S, et al. (2013). Epoxyeicosatrienoic acids (EETs) regulate epithelial sodium channel activity by extracellular signal-regulated kinase-1/2 (ERK1/2)-mediated phosphorylation. J Biol Chem 288:5223–5231.
  • 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.
  • Potente M, Fisslthaler B, Busse R, Fleming I. (2003). 11,12-Epoxyeicosatrienoic acid-induced inhibition of FOXO factors promotes endothelial proliferation by down-regulating p27Kip1. J Biol Chem 278:29619–29625.
  • Potente M, Michaelis UR, Fisslthaler B, et al. (2002). Cytochrome P450 2C9-induced endothelial cell proliferation involves induction of mitogen-activated protein (MAP) kinase phosphatase-1, inhibition of the c-Jun N-terminal kinase, and up-regulation of cyclin D1. J Biol Chem 277:15671–15676.
  • 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.
  • Rifkind AB, Lee C, Chang TK, 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.
  • Rong X, Li Y, Ebihara K, et al. (2010). Angiotensin II type 1 receptor-independent beneficial effects of telmisartan on dietary-induced obesity, insulin resistance and fatty liver in mice. Diabetologia 53:1727–1731.
  • Rupec RA, Baeuerle PA. (1995). The genomic response of tumor cells to hypoxia and reoxygenation. Differential activation of transcription factors AP-1 and NF-κB. Eur J Biochem 234:632–640.
  • 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.
  • 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.
  • Sisignano M, Park CK, Angioni C, et al. (2012). 5,6-EET is released upon neuronal activity and induces mechanical pain hypersensitivity via TRPA1 on central afferent terminals. J Neurosci 32:6364–6372.
  • 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 Genom 18:943–953.
  • Snider NT, Sikora MJ, Sridar C, et al. (2008). The endocannabinoid anandamide is a substrate for the human polymorphic cytochrome P450 2D6. J Pharmacol Exp Ther 327:538–545.
  • Spector AA, Kim HY. (2015). Cytochrome P450 epoxygenase pathway of polyunsaturated fatty acid metabolism. Biochim Biophys Acta 1851:356–365.
  • 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.
  • Stupans I, Murray M, Kirlich A, et al. (2001). Inactivation of cytochrome P450 by the food-derived complex phenol oleuropein glycoside. Food Chem Toxicol 39:1119–1124.
  • Tak PP, Firestein GS. (2001). NF-κB: A key role in inflammatory diseases. J Clin Invest 107:7–11.
  • Thum T, Erpenbeck VJ, Moeller J, et al. (2006). Expression of xenobiotic metabolizing enzymes in different lung compartments of smokers and nonsmokers. Environ Health Perspect 114:1655–1661.
  • Treisman R. (1996). Regulation of transcription by MAP kinase cascades. Curr Opin Cell Biol 8:205–215.
  • Vander Haar E, Lee SI, Bandhakavi S, et al. (2007). Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nat Cell Biol 9:316–323.
  • Wamberg L, Christiansen T, Paulsen SK, et al. (2013). Expression of vitamin D-metabolizing enzymes in human adipose tissue – the effect of obesity and diet-induced weight loss. Int J Obes (Lond) 37:651–657.
  • 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 γ 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 P, Zweier JL. (1996). Measurement of nitric oxide and peroxynitrite generation in the postischemic heart. Evidence for peroxynitrite-mediated reperfusion injury. J Biol Chem 271:29223–29230.
  • Wang X, Ni L, Yang L, et al. (2014). CYP2J2-derived epoxyeicosatrienoic acids suppress endoplasmic reticulum stress in heart failure. Mol Pharmacol 85:105–115.
  • Watanabe H, Vriens J, Prenen J, et al. (2003). Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels. Nature 424:434–438.
  • 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.
  • Wong WK, Ou XM, Chen K, Shih JC. (2002). Activation of human monoamine oxidase B gene expression by a protein kinase C MAPK signal transduction pathway involves c-Jun and Egr-1. J Biol Chem 277:22222–22230.
  • 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.
  • Xu H, Murray M, McLachlan AJ. (2009). Influence of genetic polymorphisms on the pharmacokinetics and pharmacodynamics of sulfonylurea drugs. Curr Drug Metab 10:643–658.
  • Xu X, Zhao CX, Wang L, et al. (2010). Increased CYP2J3 expression reduces insulin resistance in fructose-treated rats and db/db mice. Diabetes 59:997–1005.
  • Xu Y, Ding H, Peng J, et al. (2011). Association between polymorphisms of CYP2J2 and EPHX2 genes and risk of coronary artery disease. Pharmacogenet Genomics 21:489–494.
  • Yamazaki H, Gillam EM, Dong MS, et al. (1997). Reconstitution of recombinant cytochrome P450 2C10(2C9) and comparison with cytochrome P450 3A4 and other forms: Effects of cytochrome P450-P450 and cytochrome P450-b5 interactions. Arch Biochem Biophys 342:329–337.
  • Yamazaki H, Okayama A, Imai N, et al. (2006). Inter-individual variation of cytochrome P4502J2 expression and catalytic activities in liver microsomes from Japanese and Caucasian populations. Xenobiotica 36:1201–1209.
  • 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.
  • Yang S, Lin L, Chen JX, et al. (2007). Cytochrome P-450 epoxygenases protect endothelial cells from apoptosis induced by tumor necrosis factor-α via MAPK and PI3K/Akt signaling pathways. Am J Physiol Heart Circ Physiol 293:H142–H151.
  • 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.
  • 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.
  • 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 138:1338–13346.
  • 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. (2001). Epoxygenase pathways of arachidonic acid metabolism. J Biol Chem 276:36059–36062.
  • Zhang C, Harder DR. (2002). Cerebral capillary endothelial cell mitogenesis and morphogenesis induced by astrocytic epoxyeicosatrienoic acid. Stroke 33:2957–2964.
  • Zhang G, Panigrahy D, Mahakian LM, et al. (2013). Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis. Proc Natl Acad Sci USA 110:6530–6535.
  • 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. (1999). Induction of rat small intestinal cytochrome P-450 2J4. Drug Metab Dispos 27:1123–1127.
  • Zhang S, Chen G, Li N, et al. (2015). CYP2J2 overexpression ameliorates hyperlipidemia via increased fatty acid oxidation mediated by the AMPK pathway. Obesity 2:1401–1413.
  • Zhang Y, El-Sikhry H, Chaudhary KR, et al. (2009). Overexpression of CYP2J2 provides protection against doxorubicin-induced cardiotoxicity. Am J Physiol Heart Circ Physiol 297:H37–H46.
  • Zhao X, Dey A, Romanko OP, et al. (2005). Decreased epoxygenase and increased epoxide hydrolase expression in the mesenteric artery of obese Zucker rats. Am J Physiol Regul Integr Comp Physiol 288:R188–R196.
  • Zhao X, Pollock DM, Inscho EW, et al. (2003). Decreased renal cytochrome P450 2C enzymes and impaired vasodilation are associated with angiotensin salt-sensitive hypertension. Hypertension 41:709–714.
  • 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.

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.