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Gene Review

CYP2J2  -  cytochrome P450, family 2, subfamily J,...

Homo sapiens

Synonyms: Arachidonic acid epoxygenase, CYPIIJ2, Cytochrome P450 2J2
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Disease relevance of CYP2J2

  • Recombinant human CYP2J2 was overexpressed in Escherichia coli, purified, and assayed for vitamin D 25-hydroxylation activity [1].
  • We hypothesized that functionally relevant polymorphisms in the CYP2J2 or CYP2C8 genes influence hypertension risk [2].
  • Recombinant CYP2J2 protein was prepared using the baculovirus expression system and purified to near electrophoretic homogeneity [3].
  • Activation of c-Fos expression by hypoxia promotes the formation of c-Jun/c-Fos heterodimers, which decrease the binding of c-Jun to the CYP2J2 upstream region, leading to gene down-regulation [4].
  • CYP2J2 Tr hearts have improved recovery of left ventricular developed pressure (LVDP) compared with wild-type (WT) hearts after 20 minutes ischemia and 40 minutes reperfusion [5].

Psychiatry related information on CYP2J2


High impact information on CYP2J2

  • The cytochrome P450 isoform CYP2J2 was cloned and identified as a potential source of EETs in human endothelial cells [7].
  • Examination of signaling pathways on the effects of CYP2J2 and EETs revealed activation of mitogen-activated protein kinases and PI3 kinase-AKT systems and elevation of epithelial growth factor receptor phosphorylation level [8].
  • In this study, we found that very strong and selective CYP2J2 expression was detected in human carcinoma tissues in 101 of 130 patients (77%) as well as eight human carcinoma cell lines but undetectable in adjacent normal tissues and nontumoric human cell lines by Western, reverse transcription-PCR, and immunohistochemical staining [8].
  • Cytochrome P450 2J2 promotes the neoplastic phenotype of carcinoma cells and is up-regulated in human tumors [8].
  • These findings indicate that EETs possess fibrinolytic properties through the induction of t-PA and suggest that endothelial CYP2J2 may play an important role in regulating vascular hemostasis [9].

Chemical compound and disease context of CYP2J2


Biological context of CYP2J2


Anatomical context of CYP2J2


Associations of CYP2J2 with chemical compounds

  • CYP2J2 was selected as a candidate expressed in the intestine and closely related to arachidonic acid metabolism [13].
  • The CYP2C inhibitor sulfaphenazole depressed human liver microsomal epoxygenase activity by 50% at 50 microM, while alpha-naphthoflavone inhibited arachidonic acid epoxygenase activity by 27% at 2 microM and by 32% at 10 microM [17].
  • Immunohistochemical analysis of formalin-fixed paraffin-embedded human and rat lung sections using the anti-human CYP2J2 IgG and avidin/biotin/peroxidase detection showed that CYP2J proteins were primarily expressed in ciliated epithelial cells lining the airway [18].
  • The ability of these variants to metabolize arachidonic acid and linoleic acid was compared with that of wild-type CYP2J2 [19].
  • HR resulted in cell injury, as indicated by significant increases in lactate dehydrogenase (LDH) release and trypan blue stained cells (p < 0.01) and was associated with a decrease in CYP2J2 protein expression [12].

Regulatory relationships of CYP2J2


Other interactions of CYP2J2


Analytical, diagnostic and therapeutic context of CYP2J2


  1. Characterization of rat and human CYP2J enzymes as Vitamin D 25-hydroxylases. Aiba, I., Yamasaki, T., Shinki, T., Izumi, S., Yamamoto, K., Yamada, S., Terato, H., Ide, H., Ohyama, Y. Steroids (2006) [Pubmed]
  2. Single nucleotide polymorphisms in the CYP2J2 and CYP2C8 genes and the risk of hypertension. King, L.M., Gainer, J.V., David, G.L., Dai, D., Goldstein, J.A., Brown, N.J., Zeldin, D.C. Pharmacogenet. Genomics (2005) [Pubmed]
  3. Molecular cloning and expression of CYP2J2, a human cytochrome P450 arachidonic acid epoxygenase highly expressed in heart. Wu, S., Moomaw, C.R., Tomer, K.B., Falck, J.R., Zeldin, D.C. J. Biol. Chem. (1996) [Pubmed]
  4. Role of activator protein-1 in the down-regulation of the human CYP2J2 gene in hypoxia. Marden, N.Y., Fiala-Beer, E., Xiang, S.H., Murray, M. Biochem. J. (2003) [Pubmed]
  5. Enhanced postischemic functional recovery in CYP2J2 transgenic hearts involves mitochondrial ATP-sensitive K+ channels and p42/p44 MAPK pathway. Seubert, J., Yang, B., Bradbury, J.A., Graves, J., Degraff, L.M., Gabel, S., Gooch, R., Foley, J., Newman, J., Mao, L., Rockman, H.A., Hammock, B.D., Murphy, E., Zeldin, D.C. Circ. Res. (2004) [Pubmed]
  6. Variability of CYP2J2 Expression in Human Fetal Tissues. Gaedigk, A., Baker, D.W., Totah, R.A., Gaedigk, R., Pearce, R.E., Vyhlidal, C.A., Zeldin, D.C., Leeder, J.S. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  7. Anti-inflammatory properties of cytochrome P450 epoxygenase-derived eicosanoids. Node, K., Huo, Y., Ruan, X., Yang, B., Spiecker, M., Ley, K., Zeldin, D.C., Liao, J.K. Science (1999) [Pubmed]
  8. Cytochrome P450 2J2 promotes the neoplastic phenotype of carcinoma cells and is up-regulated in human tumors. Jiang, J.G., Chen, C.L., Card, J.W., Yang, S., Chen, J.X., Fu, X.N., Ning, Y.G., Xiao, X., Zeldin, D.C., Wang, D.W. Cancer Res. (2005) [Pubmed]
  9. Activation of Galpha s mediates induction of tissue-type plasminogen activator gene transcription by epoxyeicosatrienoic acids. Node, K., Ruan, X.L., Dai, J., Yang, S.X., Graham, L., Zeldin, D.C., Liao, J.K. J. Biol. Chem. (2001) [Pubmed]
  10. Characterization of Ebastine, Hydroxyebastine, and Carebastine Metabolism by Human Liver Microsomes and Expressed Cytochrome P450 Enzymes: Major Roles for CYP2J2 and CYP3A. Liu, K.H., Kim, M.G., Lee, D.J., Yoon, Y.J., Kim, M.J., Shon, J.H., Choi, C.S., Choi, Y.K., Desta, Z., Shin, J.G. Drug Metab. Dispos. (2006) [Pubmed]
  11. Molecular cloning, expression, and functional significance of a cytochrome P450 highly expressed in rat heart myocytes. Wu, S., Chen, W., Murphy, E., Gabel, S., Tomer, K.B., Foley, J., Steenbergen, C., Falck, J.R., Moomaw, C.R., Zeldin, D.C. J. Biol. Chem. (1997) [Pubmed]
  12. Overexpression of cytochrome P450 CYP2J2 protects against hypoxia-reoxygenation injury in cultured bovine aortic endothelial cells. Yang, B., Graham, L., Dikalov, S., Mason, R.P., Falck, J.R., Liao, J.K., Zeldin, D.C. Mol. Pharmacol. (2001) [Pubmed]
  13. Involvement of CYP2J2 and CYP4F12 in the metabolism of ebastine in human intestinal microsomes. Hashizume, T., Imaoka, S., Mise, M., Terauchi, Y., Fujii, T., Miyazaki, H., Kamataki, T., Funae, Y. J. Pharmacol. Exp. Ther. (2002) [Pubmed]
  14. Detection of Human CYP2C8, CYP2C9, and CYP2J2 in Cardiovascular Tissues. Delozier, T.C., Kissling, G.E., Coulter, S.J., Dai, D., Foley, J.F., Bradbury, J.A., Murphy, E., Steenbergen, C., Zeldin, D.C., Goldstein, J.A. Drug Metab. Dispos. (2007) [Pubmed]
  15. Cytochrome P450 CYP2J9, a new mouse arachidonic acid omega-1 hydroxylase predominantly expressed in brain. Qu, W., Bradbury, J.A., Tsao, C.C., Maronpot, R., Harry, G.J., Parker, C.E., Davis, L.S., Breyer, M.D., Waalkes, M.P., Falck, J.R., Chen, J., Rosenberg, R.L., Zeldin, D.C. J. Biol. Chem. (2001) [Pubmed]
  16. CYP2J subfamily cytochrome P450s in the gastrointestinal tract: expression, localization, and potential functional significance. Zeldin, D.C., Foley, J., Goldsworthy, S.M., Cook, M.E., Boyle, J.E., Ma, J., Moomaw, C.R., Tomer, K.B., Steenbergen, C., Wu, S. Mol. Pharmacol. (1997) [Pubmed]
  17. 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. Rifkind, A.B., Lee, C., Chang, T.K., Waxman, D.J. Arch. Biochem. Biophys. (1995) [Pubmed]
  18. CYP2J subfamily P450s in the lung: expression, localization, and potential functional significance. Zeldin, D.C., Foley, J., Ma, J., Boyle, J.E., Pascual, J.M., Moomaw, C.R., Tomer, K.B., Steenbergen, C., Wu, S. Mol. Pharmacol. (1996) [Pubmed]
  19. Cloning of CYP2J2 gene and identification of functional polymorphisms. King, L.M., Ma, J., Srettabunjong, S., Graves, J., Bradbury, J.A., Li, L., Spiecker, M., Liao, J.K., Mohrenweiser, H., Zeldin, D.C. Mol. Pharmacol. (2002) [Pubmed]
  20. Identification and functional characterization of novel CYP2J2 variants: G312R variant causes loss of enzyme catalytic activity. Lee, S.S., Jeong, H.E., Liu, K.H., Ryu, J.Y., Moon, T., Yoon, C.N., Oh, S.J., Yun, C.H., Shin, J.G. Pharmacogenet. Genomics (2005) [Pubmed]
  21. Expression of biotransformation enzymes in human fetal olfactory mucosa: potential roles in developmental toxicity. Gu, J., Su, T., Chen, Y., Zhang, Q.Y., Ding, X. Toxicol. Appl. Pharmacol. (2000) [Pubmed]
  22. Cardiac and vascular KATP channels in rats are activated by endogenous epoxyeicosatrienoic acids through different mechanisms. Lu, T., Ye, D., Wang, X., Seubert, J.M., Graves, J.P., Bradbury, J.A., Zeldin, D.C., Lee, H.C. J. Physiol. (Lond.) (2006) [Pubmed]
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